Cleveland placed its leading tackler on injured reserve Tuesday, two days after he damaged his shoulder during the first half of a 27-14 loss at Pittsburgh.
"It's disappointing any time you lose a player for the season, and this is especially true with someone like D'Qwell, who has proven to be an outstanding leader for us both on and off the field," Browns coach Eric Mangini said in a statement.
Jackson got hurt in the second quarter on Sunday. He faces possible surgery.
Though undersized at 6-foot, 240 pounds, Jackson has been one of Cleveland's best defenders over the past three-plus seasons.
Jackson led the NFL with 188 tackles last season and was chosen as a Pro Bowl alternate. A second-round pick in 2006, Jackson is eligible for free agency after this season. He had been trying to get a new contract from the Browns, who might have to play rookies David Veikune and Kaluka Maiava at inside linebacker in their 3-4 scheme.
Jackson has led the Browns in tackles the past two seasons and was second as a rookie in 2006. He had 57 tackles -- 44 solos -- this season and was credited with two broken-up passes and a forced fumble.
The 26-year-old Jackson was selected as a defensive captain before the season.