When accepting his award, Franco, who is nominated for Best Actor at Sunday's Oscars for his 127 Hours role, thanked his agent, manager and publicist, who told him to take a break from school, saying, "James, you're an effing idiot if you don't do this movie."
After winning the Golden Globe and Screen Actors Guild Award for her role in Black Swan, Natalie Portman also won the Spirit Award for best female lead. Black Swan also won for best film, and Darren Aronofsky took best director.
In what could be a precursor to the big show on Sunday, The King's Speech, the Oscar Best Picture front-runner, won for best foreign film. Meanwhile, Oscar underdog John Hawkes won for best male supporting for his role in Winter's Bone.
Check out a full list of winners:
Best Film: Black Swan
Best Director: Darren Aronofsky, Black Swan
Best Female Lead: Natalie Portman, Black Swan
Best Male Lead: James Franco, 127 Hours
Best Female Supporting: Dale Dickey, Winter's Bone
Best Male Supporting: John Hawkes, Winter's Bone
Best Screenplay: Stuart Blumberg, Lisa Cholodenko, The Kids Are All Right
Best First Screenplay: Tiny Furniture, Lena Dunham
Best First Feature: Get Low, Aaron Schneider
Best Cinematography: Matthew Libatique, Black Swan
Best Documentary: Exit Through the Gift Shop, Banksy
Best Foreign Film: The King's Speech, Tom Hooper