Dudek will have surgery next week after tearing the ACL last Saturday in a non-contact drill, Smith said. The severity of the injury was confirmed Friday.
"The game sometimes can be cruel," Smith said. "It's unfortunate. The guy worked himself pretty hard to get back in position."
Dudek was not available for comment, but posted a Bible verse on Twitter feed late Friday, after Smith confirmed the news.
"Do not be afraid; do not be discouraged, for the Lord your God will be with you wherever you go"— Mikey Dudek (@MDFlash_7) April 9, 2016
Dudek suffered the same injury during spring drills last April and missed the 2015 season, his sophomore year.
In 2014, Dudek was a freshman All American and Illinois' top receiver and offensive threat. He had 76 catches for 1,038 yards. He also tied College Football Hall of Famer David Williams for the Illinois freshman record with six touchdown catches.
A week into spring practice, Smith said it's too soon to know who will emerge as quarterback Wes Lunt's top target with Dudek out.
"It's an opportunity for someone. That's how they should look at it," Smith said.