The In Da Club hitmaker plays an American footballer who is diagnosed with cancer in the film, which he wrote based on a friend's tragic battle with the disease.
The hip-hop star, who survived on a liquid diet, lost 54 pounds for the role and stunned fans earlier this week when he posted photos of his skeletal image online.
In an accompanying post, titled '50 Cent's Shocking Slim-Down!', 50 Cent wrote, "I lost 54 pounds for it. I was starving."
But the rapper refused to let his hunger pains steer him off course and turned to other actors who had famously lost weight for films whenever he found his spirit diminishing.
He tells the Associated Press, "I actually got on the computer. When it started getting difficult, I was looking to see what their experience was like and I got a chance to see all of the interviews they had at different time periods when they were doing promotion for the projects."
De Niro shed 35 pounds to play Travis Bickle in 1976 classic Taxi Driver, while Hanks lost the same amount of weight for his Oscar-winning role as a gay lawyer with AIDS in 1993 drama Philadelphia.
Bale went even further and dropped an astonishing 63 pounds in a matter of months to achieve his emaciated appearance in 2004's The Machinist.