The team said his return was questionable.
Stafford's hand appeared to get hit by an Oakland defender after throwing an incomplete pass. Trainers were examining Stafford's hand on the sideline. He was 8 for 10 for 68 yards.
Shaun Hill took over at quarterback on Detroit's next possession.
Detroit drafted Stafford No. 1 overall in 2009 out of Georgia. After a right shoulder injury sidelined him for all but three games in 2010, Stafford threw for 5,038 yards and 41 touchdowns last season to lead the Lions to the playoffs, where they lost to New Orleans in the division round.