The former Lucasian professor of mathematics at Cambridge University is the latest celebrity to star in the website's adverts, where well-known figures plot to destroy fictitious opera singer Gio Compario and silence his irritating sales slogan.
The advert sees 70-year-old Professor Hawking announce to a packed lecture theatre that he has discovered how to generate a super massive black hole, before being asked what he will do with the knowledge.
The scene then cuts to the opera singer - played by Wynne Evans - haranguing a couple in the street, before a black hole forms behind him and sucks him in.
The wheelchair-bound scientist, well known for speaking using a computerised voice because of his motor neurone disease, is then shown laughing.
Professor Hawking, now director of research at Cambridge's Centre for Theoretical Cosmology, said: "I confess I am a fan of the Gocompare.com adverts, but I am also an opera fan, so I was delighted to be given the opportunity to help save the nation and silence Gio.
"I hope the public find it as funny as I did."
He joins a list of celebrities who have starred in the adverts this year which show people attempting to do away with the moustachioed tenor.