Guillermo was involved in a project called InSane for THQ - but the company went bust - and then joined Hideo Kojima for Silent Hills before the Metal Gear Solid director left Konami.
Guillermo, 50, described himself as the "albatross of video games" and joked that if he attempted to make another game, World War 3 would probably break out, reported Digital Spy.
"I joined THQ, and THQ goes broke. I join Kojima, and Kojima leaves Konami. I have decided, in order not to destroy anyone else's life, I have decided I will never again get involved in video games. Otherwise, I'll join someone and his house will explode, or something," he said.
The filmmaker previously suggested that he was working on a new project with Hideo Kojima, but failed to offer any additional information.
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