Kiffin, 38, was informed of the decision by athletic director Pat Haden early in the morning after the team arrived back in Los Angeles.
The team lost seven of its past 11 games. The Trojans are 3-2 this year and have lost both of its Pac-12 games. Kiffin's overall record at USC is 28-15 over the course of four years.
Since Kiffin took over the job after previous head coach Pete Carroll left to coach the NFL's Seattle Seahawks, the team has had to deal with NCAA sanctions that included the loss of 30 scholarships over the course of three years. The school was also banned from bowl games for two years due to rules violations during Carroll's tenure.