Winfrey, 62, has long been involved with the project, adapted from Rebecca Skloot's 2010 book of the same name.
The media mogul signed on as an executive producer when the book's film rights were first acquired in 2010, and the network announced on Monday that she will star in the biopic as well as co-executive producing it with Skloot and True Blood creator Alan Ball.
The movie, set to begin filming this summer, centers on the true story of Henrietta Lacks, an African-American woman whose cervical cancer cells were used to create the first immortal human cell line, HeLa, in 1951.
The story is told from the perspective of Winfrey's character, protagonist Deborah Lacks, who explores how the unlicensed harvesting of her mother's cancerous cells led to unprecedented medical breakthroughs.
Winfrey made her big-screen debut in Steven Spielberg's The Color Purple, which earned her an Oscar nomination in 1986. In recent years, she has starred as a supporting actress in Selma and Lee Daniels' The Butler.
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Winfrey also has a recurring role on the upcoming drama Greenleaf.
Henrietta Lacks' sons Zakariyya Rahman and David Lacks, Jr., as well as granddaughter Jeri Lacksare will serve as consultants on the HBO project.
A premiere date for the movie has not yet been announced, but in the meantime, Winfrey fans can get their hands on their very own piece of the iconic Oprah Winfrey Show – beginning Thursday at 3 p.m., a select number of studio audience chairs will be available for auction via ScreenBid, with net proceeds going to the Oprah Winfrey Leadership Academy Foundation.