The team announced Wednesday afternoon that Kalil has been placed on injured reserve and will miss the rest of the season. Coach Ron Rivera told the media Kalil has a Lisfranc injury that will require surgery.
Kalil suffered the foot injury in Sunday's 16-12 loss to Seattle.
He went to see Dr. Robert Anderson on Tuesday, and it was determined he had a Lisfranc injury, having torn a ligament that supports the middle of his foot. He will have season-ending surgery Monday.
A first-round draft pick by the Panthers in 2007, Kalil has been to the past three Pro Bowls and is a key cog in Carolina's offense.
Rivera firmly endorsed Kalil's preseason Super Bowl prediction and even had shirts printed up for the players that read: "I've got Ryan Kalil's back."
The Panthers have a bye this week and will have to scramble to replace Kalil.
"He is most certainly one of the emotional leaders, and it's hard to replace those kind of guys," Rivera said. "The truth of the matter is it's time for us as a team to step up. This is another one of those things that's going to try us."
The Panthers also may look to sign a center for depth.
Information from The Associated Press was used in this report.