Illinois coach John Groce said the second-round game in the winner's bracket of the tournament would be a "great challenge" for his players.
"They've been in plenty of intimidating environments, I can assure you. We know (Tuesday) will be one," Groce said.
Illinois made USC look inferior hours after Chaminade knocked off Texas.
Brandon Paul scored 26 points and Illinois used a hot first half to ride to an easy 94-64 win.
Illinois shot just under 69 percent in the first half on its way to a 31-point lead at the break. USC pulled no closer than 18 points in the second half despite some sloppy play from Illinois, which finished with 20 turnovers.
The Illini (4-0), who never trailed, also got 13 points from DJ Richardson and 10 from Tyler Griffey. Tracy Abrams had 11 points and eight assists, one more than the entire Trojans team.
"We came out, got off to a great start, had a lot of energy, really moved the ball. It was a free-flowing first half," Groce said. "I thought the tempo was to our liking."
Up 9-8 roughly five minutes into the game, Illinois outscored USC 21-3 over the next six minutes. The Illini boosted their lead to 34 just after halftime on a 3-pointer from Griffey and were never seriously threatened.
USC (2-1) was led by Eric Wise with 13 points. J.T. Terrell added 11 and Jio Fontan had 10—eight in the first half.
"Tonight, we didn't do anything. We got set back on our heels," USC coach Kevin O'Neill said. "Once they started making shots, their confidence grew and ours went down."
Illinois badly outrebounded USC 42-20, grabbing as many offensive rebounds (15) as USC had defensive rebounds.
The Illini were playing their second game in Hawaii during the trip after beating Hawaii in Oahu on Friday in overtime.
USC failed in its bid to go undefeated in its first three games for the first time in 11 years.
"The way we played, I certainly hope that's not indicative of our team. Tonight, we didn't do anything we wanted to do offensively or defensively," O'Neill said. "I've been at SC for four years now and we've never got beaten that bad, and we had a bad team last year and we didn't get beat that bad."
Oskar Garcia can be reached on Twitter at http://twitter.com/oskargarcia.