The fourth-year veteran tore the anterior cruciate ligament of his right knee while trying to make a tackle on a running play. He is scheduled for Wednesday season-ending surgery and will be placed on injured reserve.
It was not immediately certain who will replace Kelly in the lineup. The leading candidate is believed to be rookie Jay Richardson, a fifth-round draft choice.
Kelly, 26, has been a versatile and productive defender for the Raiders, who signed him as an undrafted college free agent in 2004. After contributing as a rotational backup in his rookie year, the former Mississippi State standout moved into a starting spot in his second season, playing mostly at tackle, and he has been a fixture in the lineup ever since.
He developed into one of the NFL's better pass-rushing tackles, but eventually moved to the strongside end position to help anchor against the run, and has been effective there. In seven games this season, Kelly has 30 tackles and one sack.
For his career, Kelly has registered 166 tackles, 13 sacks, seven forced fumbles, one fumble recovery, and five passes defensed. He has appeared in 49 games and started in 38 of them.
The injury could somewhat muddy Kelly's future, since he is eligible for unrestricted free agency after this season, and figured to draw good interest in the market before the injury. Kelly is expected, however, to be fully rehabilitated well in advance of the start of training camp next summer.
Len Pasquarelli covers the NFL for ESPN.com.