MacFarlane said he believes that the show, which has just finished its 10th series, has been running for too long.
And he added that he is “secretly hoping” that fans will grow tired of the animated show, which follows the everyday life of the Griffin family.
The 37-year-old writer, who is also the brains behind several other US cartoon shows including American Dad! and The Cleveland Show, told The Hollywood Reporter: 'Part of me thinks that Family Guy should have already ended. I think seven seasons is about right.
'I talk to the fans and, in a way, I'm kind of secretly hoping for them to say we're done with it.
'There are plenty of people who say the show is kind of over-the-hill, but still the vast majority go pale in the face when I mention the possibility.'
He added that he would prefer to end the show and instead release a movie every few years.