Polamalu hasn't practiced all week after missing Sunday's game against the New York Jets.
Polamalu leads the Steelers with six interceptions, one of which he has returned for a touchdown. He also has a sack and a fumble recovery to go with 62 tackles.
A source told NFL Network insider Jason La Canfora last week that the team isn't considering putting the five-time Pro Bowl selection on season-ending injured reserve and expects to have him back for the playoffs.
If the Steelers (10-4) beat the Panthers on Thursday and the Cleveland Browns (5-9) on Jan. 2, they will win the AFC North and be seeded No. 2 in the playoffs, no matter what the Baltimore Ravens (10-4) do against the Browns and Cincinnati Bengals (3-11).
That's all the incentive the Steelers need to play their second game in five days, a challenge for a beaten-up team regardless of its opponent.
Wide receiver Arnaz Battle (chest) and defensive end Aaron Smith (triceps) also have been ruled out for the game, the Steelers announced Wednesday. Defensive tackle Steve McLendon (stinger) is probable.
There is no question that Polamalu's status is central to the Steelers' playoff destiny.
"This guy has intuition, has innate awareness and ability," coach Mike Tomlin told the team's official website Tuesday. "He probably trusts his more than anybody else I've ever been around. When he makes a decision to take a calculated risk, he's 10 toes in on it. He's full steam ahead."
The Steelers, who rank 24th in pass defense in the NFL, often have trouble defending teams with strong passing games, but that's certainly not Carolina. The Panthers' average of 149.3 passing yards is 32 per game fewer than any other team, and rookie quarterback Jimmy Clausen has thrown seven interceptions but just two touchdown passes.
What the Steelers probably worry about most is another injury to a key starter, just when they're hopeful Polamalu and defensive end Aaron Smith (triceps) might be healthy for their first playoff game.
The Associated Press contributed to this report.