EXCLUSIVE: Rose Byrne talks returning to work after giving birth, telling Oprah Winfrey to 'shut the **** up!'

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It's no secret that Oprah Winfrey is a legend, but it turns out that even legends can get intimidated! The media mogul and former talk show host admitted that she was nervous to be acting alongside top tier actors in HBO's upcoming film, The Immortal Life of Henrietta Lacks.

WATCH: Reese Witherspoon Dishes on What It's Like to Make a Movie With Oprah Winfrey: 'She'd Do the Voice!'

Co-star Rose Byrne called this revelation "very strange," when speaking with ET's Jennifer Peros at the premiere of the film.

"Yeah, very strange. She's incredibly humble for someone of her, being a living legend really," Byrne said. "She had a huge undertaking and she was nervous admittedly, as was I. It's a very important story and a big story we tried to tell in a short amount of time too so it was ambitious."

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Oprah through the years
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Oprah Winfrey speaks during the unveiling ceremony of the Maya Angelou Forever Stamp at the Warner Theater in Washington, DC, on April 7, 2015. AFP PHOTO/NICHOLAS KAMM (Photo credit should read NICHOLAS KAMM/AFP/Getty Images)
HOLLYWOOD, CA - FEBRUARY 22: Oprah Winfrey attends the 87th Annual Academy Awards at Dolby Theatre on February 22, 2015 in Hollywood, California. (Photo by Christopher Polk/Getty Images)
SANTA MONICA, CA - FEBRUARY 21: Oprah Winfrey speaks onstage during the 2015 Film Independent Spirit Awards at Santa Monica Beach on February 21, 2015 in Santa Monica, California. (Photo by Kevork Djansezian/Getty Images)
PASADENA, CA - FEBRUARY 06: (L-R) Actress Carmen Ejogo, actress/producer Oprah Winfrey and director/producer Ava DuVernay accept the award for Outstanding Motion Picture for 'Selma', onstage during the 46th NAACP Image Awards presented by TV One at Pasadena Civic Auditorium on February 6, 2015 in Pasadena, California. (Photo by Frederick M. Brown/Getty Images for NAACP Image Awards)
Actress/producer Oprah Winfrey arrives for the Oscars Nominees' Luncheon hosted by the Academy of Motion Picture Arts and Sciences, February 2, 2015 at the Beverly Hilton Hotel in Beverly Hills, California. The 87th Oscars will take place in Hollywood, California February 22, 2015. AFP PHOTO / ROBYN BECK (Photo credit should read ROBYN BECK/AFP/Getty Images)
SELMA, AL - JANUARY 18: 'Selma' director Ava DuVernay, actor David Oyelowo, and producer/actress Oprah Winfrey participate in the ceremony to commemorate the life of Dr. Martin Luther King, Jr. on January 18, 2015 in Selma, Alabama. (Photo by David A. Smith/Getty Images)
LOS ANGELES, CA - JANUARY 15: (EXCLUSIVE COVERAGE) Actors David Oyelowo (L) and Oprah Winfrey attend the 20th annual Critics' Choice Movie Awards at the Hollywood Palladium on January 15, 2015 in Los Angeles, California. (Photo by Jason Kempin/Getty Images for A&E Network)
BEVERLY HILLS, CA - JANUARY 09: (EDITORS NOTE: IMAGE WAS SHOT IN BLACK AND WHITE) Actors Miles Teller (L) and Oprah Winfrey attend the 15th Annual AFI Awards at Four Seasons Hotel Los Angeles at Beverly Hills on January 9, 2015 in Beverly Hills, California. (Photo by Frazer Harrison/Getty Images for AFI)
SANTA BARBARA, CA - DECEMBER 06: Oprah Winfrey attends the 'Selma' and the Legends Who Paved the Way gala at Bacara Resort on December 6, 2014 in Goleta, California. (Photo by Jason Merritt/Getty Images)
NEWARK, NJ - SEPTEMBER 27: Oprah Winfrey attends the Oprah's The Life You Want Weekend - Day 2 at Prudential Center on September 27, 2014 in Newark, New Jersey. (Photo by Dave Kotinsky/Getty Images)
NEWARK, NJ - SEPTEMBER 26: Oprah Winfrey speaks at the Oprah's The Life You Want Weekend - Day 1 at Prudential Center on September 26, 2014 in Newark, New Jersey. (Photo by Dave Kotinsky/Getty Images)
PASADENA, CA - FEBRUARY 22: Oprah Winfrey speaks onstage during the 45th NAACP Image Awards presented by TV One at Pasadena Civic Auditorium on February 22, 2014 in Pasadena, California. (Photo by Kevin Winter/Getty Images for NAACP Image Awards)
LONDON, ENGLAND - FEBRUARY 16: Presentater Oprah Winfrey poses in the winners room at the EE British Academy Film Awards 2014 at The Royal Opera House on February 16, 2014 in London, England. (Photo by Anthony Harvey/Getty Images)
LOS ANGELES, CA - JANUARY 18: Actress-TV personality Oprah Winfrey in the audience during the 20th Annual Screen Actors Guild Awards at The Shrine Auditorium on January 18, 2014 in Los Angeles, California. (Photo by Kevork Djansezian/Getty Images)
SANTA MONICA, CA - JANUARY 16: Actress Oprah Winfrey attends the 19th Annual Critics' Choice Movie Awards at Barker Hangar on January 16, 2014 in Santa Monica, California. (Photo by Christopher Polk/Getty Images)
WASHINGTON, DC - NOVEMBER 20: Oprah Winfrey attends a dinner in honor of the Medal of Freedom awardees at the Smithsonian National Museum of American History on November 20, 2013 in Washington, DC. The Presidential Medal of Freedom is the nation's highest civilian honor, presented to individuals who have made meritorious contributions to the security or national interests of the United States, to world peace, or to cultural or other significant public or private endeavors. (Photo by Kevin Dietsch-Pool/Getty Images)
US President Barack Obama chats with broadcast journalist Oprah Winfrey before presenting her with the Presidential Medal of Freedom during a ceremony in the East Room of the White House on November 20, 2013 in Washington, DC. The Medal of Freedom is the country's foremost civilian honor. AFP PHOTO/Mandel NGAN (Photo credit should read MANDEL NGAN/AFP/Getty Images)
Oprah Winfrey waves as she speaks during the Let Freedom Ring Commemoration and Call to Action to commemorate the 50th anniversary of the March on Washington for Jobs and Freedom at the Lincoln Memorial in Washington, DC on August 28, 2013. Thousands gathered on the mall on the anniversary of the march and Dr. Martin Luther King, Jr.'s famous 'I Have a Dream' speech. AFP PHOTO / Saul LOEB (Photo credit should read SAUL LOEB/AFP/Getty Images)
LOS ANGELES, CA - AUGUST 12: Oprah Winfrey attends LEE DANIELS' THE BUTLER Los Angeles premiere, hosted by TWC, Budweiser and FIJI Water, Purity Vodka and Stack Wines, held at Regal Cinemas L.A. Live on August 12, 2013 in Los Angeles, California. (Photo by Mike Windle/Getty Images for TWC)
NEW YORK, NY - AUGUST 05: Oprah Winfrey attends the press conference for The Weinstein Company's LEE DANIELS' THE BUTLER at Waldorf Astoria Hotel on August 5, 2013 in New York City. (Photo by Ben Gabbe/Getty Images for Lee Daniel's THE BUTLER)
CAMBRIDGE, MA - MAY 30: Oprah Winfrey receives an Honorary Doctor of Laws Degree at 2013 Harvard University 362nd Commencement EXercises at Harvard University on May 30, 2013 in Cambridge, Massachusetts. (Photo by Paul Marotta/Getty Images)
COLLEGE PARK, GA - MAY 20: Oprah Winfrey attends the Spelman College Commencement at Georgia International Convention Center on May 20, 2012 in College Park, Georgia. (Photo by Rick Diamond/Getty Images)
NEW YORK, NY - MARCH 09: Oprah Winfrey attends at the 3rd annual Diane Von Furstenberg awards at the United Nations on March 9, 2012 in New York City. (Photo by Andrew H. Walker/Getty Images)
US television talkshow Queen Oprah Winfrey gestures during an interview at Jaipur Literature Festival (JLF) in Jaipur on January 22, 2012. Television chatshow queen Oprah Winfrey received a rock star's welcome when she spoke on Sunday to a heaving audience of thousands of fans at the Jaipur Literature Festival in India. Winfrey, wearing a gold and red Indian outfit, told the packed crowd that her love of books had helped her education and enabled her to rise from a poor childhood in Mississippi to become one of the world's most influential women. AFP PHOTO / Prakash SINGH (Photo credit should read PRAKASH SINGH/AFP/Getty Images)
MEYERTON, HENLEY ON KLIP - JANUARY 14: Oprah Winfrey poses with the Graduates at the inaugural graduation of the class of 2011 at Oprah Winfrey Leadership Academy for Girls on January 14, 2012 in Henley on Klip, South Africa. (Photo by Michelly Rall/Getty Images)
US talk show queen Oprah Winfrey looks on as she answers to journalist's questions at her South African girls' academy on January 13, 2012 in Henley on Klip. Winfrey founded the $40-million school for girls in 2007. AFP PHOTO/ STEPHANE DE SAKUTIN (Photo credit should read STEPHANE DE SAKUTIN/AFP/Getty Images)
Oprah Winfrey winner for Favorite Talk Show Host during The 30th Annual People's Choice Awards - Press Room at Pasadena Civic Auditorium in Pasadena, California, United States. (Photo by Jeffrey Mayer/WireImage)
NASHVILLE, TN - MAY 2: Oprah Winfrey arrives at the opening of Charlie's War at the Nashville Film Festival at the Green Hills Regal Cinema May 2, 2003 in Nashville, Tennessee. Her father Vernon Winfrey has a role in the film. (Photo by Adriane Jaeckle/ Getty Images)
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Byrne was admittedly intimidated by her A-list co-star as well, saying, "Of course, someone of that profile, and [me] playing very intense roles, a journalist trying to really get in her space, you know so, and with somebody whose profile everybody wants a piece of you but we leaned heavily on George Wolf our director, he really navigated us through everything."

But once the cameras were rolling, Byrne didn't hold back. In one scene she had to yell at Winfrey's character to "shut the **** up."

"It was intense! It was a long day, but we wanted to do a good job and we were g-ed up to do it," she recalled. "It was one of those strange surreal moments in your life but that's acting you know? I think I said that to Glenn Close a few times as well so I'm clearly cornering a market, telling legendary woman to eff off."

RELATED: Oprah Winfrey and Rose Byrne Uncover Tragic Medical Mystery in the 'Immortal Life of Henrietta Lacks' Trailer

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Oprah Winfrey, 1970s. (Photo by Film Favorites/Getty Images)
A portrait of Oprah Winfrey upon becoming co anchor of Eyewitness News on WJZ, with co host Jerry Turner, Baltimore, Maryland, June 26, 1978. (Photo by Afro American Newspapers/Gado/Getty Images)
Oprah Winfrey (Photo by DMIPhoto/FilmMagic)
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Oprah Winfrey (Photo by SGranitz/WireImage)
THE TONIGHT SHOW STARRING JOHNNY CARSON -- Pictured: (l-r) Talk show host Oprah Winfrey during an interview with guest host Joan Rivers on January 27, 1986 -- (Photo by: Paul Drinkwater/NBC/NBCU Photo Bank via Getty Images)
Stedman Graham and Oprah Winfrey (Photo by Ron Galella/WireImage)
Talk show host Oprah Winfrey holds her Daytime Emmy for Outstanding Talk or Service Show Host, awarded for the Oprah Winfrey Show, 1987. (Photo by Afro American Newspapers/Gado/Getty Images)
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Even with the allure of her legendary co-star, Byrne had a hard time returning to work so soon after the birth of her son, Rocco.

"It was my first job since having my son. I didn't really particularly want to go back to work but I couldn't say no, I was like, 'I can't say no to this project,'" she said of the inspirational story. "It's exceptional and to be in service of this story is my honor."

Byrne also revealed that becoming a mom has changed her mindset when it comes to taking on new roles.

"Because you want to spend time with them, but I love to work and I want to work as well, so like any working parent, man or woman, you figure it out," she said. "I don't know, I'm figuring it out every day. I'm just as naive about that as the next. I'm still trying to figure it all out."

The Immortal Life of Hernrietta Lacks premieres on April 22 at 8 p.m. ET on HBO.

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