Kiffin had a 5-15 record since being hired last year, losing his final game 28-18 on Sunday to San Diego.
The decision on the 31-year-old Kiffin was as much about his frequent criticisms of owner Al Davis' franchise as it was the team's performance on the field. Those critiques reached a peak when Kiffin distanced himself from the defense after a blowout loss in the season opener, saying that was under coordinator Rob Ryan and Davis' control.
The Raiders said the move was made for cause, meaning they will likely try not to pay Kiffin for the remainder of his contract. He signed a two-year deal worth about $4 million with a team option for 2009 when he took over last year. Kiffin's agent, Gary Uberstine, had no comment.
The move comes a day after the St. Louis Rams let go of coach Scott Linehan, marking the second firing at the quarter point of the season. The last time a coach had been fired this early in the season was when Davis got rid of Mike Shanahan after four games in 1989.
The Raiders promoted 43-year-old offensive line coach Tom Cable to interim head coach.
The Raiders have a bye this week, so the new coach's first game will be Oct. 12 at New Orleans.
Kiffin's job security was in question as far back as January, when a dispute with Davis over whether he could replace Ryan led to the owner sending his coach a letter of resignation to sign.
Kiffin refused to sign it and the feud went on throughout the off-season as Kiffin questioned big-money signings and other personnel moves made by Davis.
The Raiders have fallen on hard times of late, with the blame going beyond one coach. Oakland has an NFL-worst 20-64 record since the start of the 2003 season, a stretch spanning the tenures of Bill Callahan, Norv Turner, Art Shell and Kiffin.