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Larry Caper rushed for 95 yards and a touchdown for Michigan State (3-3, 2-1). Glenn Winston ran for 69 yards and a score in the first half before leaving with a knee injury.
Nichol, a sophomore, started in place of Kirk Cousins, who entered the game late. Nichol was 13-for-25 with an interception.
Illinois (1-4, 0-3) had its own first-time starter at quarterback, junior Eddie McGee. Illinois coach Ron Zook made McGee the starter this week over senior Juice Williams to try to spark the sputtering Illini.
But McGee's run lasted just over 32 minutes. Zook pulled him early in the third quarter after watching him complete two of his 11 passes for 31 yards.
Williams was 7-for-17 for 109 yards and a touchdown in relief.
The Spartans turned the ball over twice and killed one of their drives with back-to-back personal foul penalties that wiped out big gains in Illinois territory.
But they were good enough to spoil Illinois' homecoming with a 17-0 lead by halftime that could have been worse.
The Spartans drove 60 yards on their opening possession and were up 7-0 after Winston's 2-yard touchdown run.
They had 14 points on the scoreboard before Illinois had a first down.
They held the ball for 22 of the game's first 30 minutes, a period during which Michigan State piled up 281 yards of offense - 149 on the ground - to the Illini's 60.
Illinois' student section showered the Illini with boos as they left the field at the half.
The Illini struggled to move the ball with McGee at quarterback, though he was saddled with bad field position.
Before starting a drive late in the third quarter at the Michigan State 30 after an interception by Tavon Wilson, the Illini had opened drives from their own 2, 9, 13, 20 (twice) and 24-yard lines.
Blair White, Nichol's favorite target Saturday, had four catches for 50 yards. But Nichol spread the ball around, hitting seven different receivers.
Winston left the game in the second quarter after his right knee buckled as he hurdled a tackler in the Spartans' backfield. He had to be helped off the field and was carted to the locker room at halftime.
Information on his injury wasn't immediately available.
