The For Coloured Girls director hit back at Lee over statements he has made claiming that Perry's films portray black people in a negative light and encouraging movie-goers to avoid supporting his projects.
"I'm so sick of hearing about damn Spike Lee," Perry told Box Office Magazine during a press conference on Tuesday. "Spike can go straight to hell! You can print that. I am sick of him talking about me.
"I am sick of him saying, 'This is a c**n, this is a buffoon'. I am sick of him talking about black people going to see movies. This is what he said, 'You vote by what you see', as if black people don't know what they want to see."
He added: "I am sick of him - he talked about Whoopi, he talked about Oprah, he talked about me, he talked about Clint Eastwood. Spike needs to shut the hell up!"
Perry recently signed to play detective Alex Cross - a popular character by writer James Patterson.