Smith was ruled out due to a knee injury for the Panthers, who feature fellow wide receivers Devin Funchess, D.J. Moore and Curtis Samuel as well as Jarius Wright and Damiere Byrd in the passing game.
The 29-year-old Smith has recorded 16 receptions for 171 yards and two touchdowns in six games with Carolina (6-2), which acquired him from the Philadelphia Eagles in the offseason.
Smith hauled in 36 receptions for 430 yards and two touchdowns with the Eagles in 2017 after signing a three-year, $15 million contract. He stepped it up in the playoffs with 13 catches for 157 yards and a score as Philadelphia went on to win its first Super Bowl title in franchise history.
Four other Panthers received questionable designations for Thursday night's game, including center Ryan Kalil (ankle). Tyler Larsen would start versus the Steelers if Kalil is unable to play.
Defensive end Mario Addison and safety Eric Reid are nursing shoulder injuries while linebacker David Mayo (groin) is also questionable for the Panthers.
Carolina takes a three-game winning streak into Pittsburgh to face the Steelers (5-2-1), who have emerged victorious in four straight.