Groening asked several questions during the fan Q&A section of the session, to the delight of the audience.
He first asked: "Have you got any advice for a struggling young animator?"
"What's Matt Groening really like", he continued.
With the audience clapping around him, Groening rounded off his trio of questions with: "Can you kiss my arse some more?"
During the Family Guy panel, it was also revealed by director and producer Peter Shin that a feature film is on the horizon, but that it is currently on hold as Seth MacFarlane directs Ted 2.
The Simpsons and Family Guy's crossover episode will premiere in September on Fox, and will see the Griffins going on a road trip to Springfield and meeting the famous yellow family.
Read Digital Spy's live blog of The Simpsons panel, celebrating 25 years of the show.