TMZ said O'Neal died Monday, but the celebrity news Web site did not report any other details regarding the cause or location of his death.
"Yes it's true that our pal Patrice O'Neal has passed away. The funniest and best thinker I've ever known PERIOD," Hughes, known as Opie on the radio, said via Twitter Tuesday.
O'Neal was a frequent guest on the "Opie and Anthony" show.
He also performed at the "Comedy Central Roast of Charlie Sheen" in September and guest starred on TV's "Chappelle Show," "The Office," and "Tough Crowd with Colin Quinn."