It is the same knee that caused Tillman to miss four games before returning to face the New York Giants on Dec. 20, at least a week earlier than planned after cornerback Bene Benwikere fractured his leg a week earlier.
Carolina coach Ron Rivera said Tillman, 34, knew the risks when he returned.
"He did," Rivera said. "Knowing him, he knew exactly what the risks were. He wanted to play, and he's done a great job for us."
Tillman sent out the following messages on Twitter shortly after learning his season and possibly his career was over.
Thanks for all the support. I really appreciate it.— Charles Tillman (@peanuttillman) January 4, 2016
It's all good everybody. We're 15-1 and have a first round bye and home field through out the playoffs. 😎😎— Charles Tillman (@peanuttillman) January 4, 2016
Tillman will be replaced as the starter by Robert McClain, who was signed on Dec. 15 after Benwikere was placed on injured reserve.
That means the Panthers (15-1) will enter their Jan. 17 divisional-round playoff game against the lowest seed to survive this week between No. 6 Seattle, No. 5 Green Bay or No. 4 Washington with two starters in the secondary who weren't on NFL rosters for much of the season.
Carolina lured Cortland Finnegan out of semi-retirement a week before signing McClain when it became apparent Tillman's injury would keep him out for an extended period. Finnegan is now the starting nickelback with Benwikere gone.
McClain hadn't been on a roster since being released by the New England Patriots at the end of training camp.
Both were a part of a tryout run by Carolina general manager Dave Gettleman and the scouting department when looking for depth to replace Tillman the first time he was injured.
Rivera is confident that the loss of Tillman won't have a huge impact on Carolina's playoff chances because of the team's next-man-up mentality. The defense continued to play at a high level when middle linebacker Luke Kuechly missed three games with a concussion, defensive end Charles Johnson was on injured reserve for seven games and Tillman was out for four.
McClain showed that next-man-up mentality on Sunday with an interception and seven tackles after Tillman was injured.
"It's a special thing around here that they've built," Finnegan said. "Just to be a part of it is a true blessing. We'll continue to pick up the pieces along the way."
"We didn't miss a beat when Robert came in."
Rivera assured that Tillman will remain around the team throughout its playoff run.
"The guy's done some good things for us," Rivera said. "But he's going to be around to be a part of what we do as we go forward."