Houston is down 28-14 to SMU after two quarters.
SMU's Taylor Reed intercepted Piland and returned it six yards for SMU's second touchdown of the second quarter and gave the Mustangs at 14-point lead at half.
Piland passed for 181 yards on 15-of-25 passing in the first half but also threw two interceptions before leaving the game after Reed's turnover.
Piland was replaced in the game by senior backup Crawford Jones, who went 2-for-2 for eight yards on Houston's final possession of the first half.
Piland has thrown for 2,084 yards, 10 touchdowns and seven interceptions while completeing 60.5 percent of his passes through six games for Houston this season. Houston is 3-3 overall and 2-0 in conference play.