De Niro introduced the movie in which he played Rupert Pupkin, an aspiring comedian who kidnaps Jerry Langford, a late night TV host, played by Lewis.
De Niro said he had not viewed the film in 25 years and hoped it wouldn't embarrass him, The Hollywood Reporter said.
The movie was released 30 years ago to mixed reviews. Roger Ebert panned it as "one of the most arid, painful, wounded movies I've ever seen," and Pauline Kael of The New Yorker said Pupkin was "Jake LaMotta without fists."
The film today is almost universally lauded and seen as having been ahead of its time as a commentary on the often negative influence of the entertainment and media worlds, THR said.
Scorsese said, "We knew we were commenting on the culture of that time, but not thinking that it would blow up into what it is now."
Scorsese was asked whether it was difficult to do comedy, to which he replied, "It wasn't a comedy, was it?"
The highlight of the event was Lewis' appearance, as he has made far fewer public appearances in recent years because of health issues and advanced age, THR said.