Smith suffered the injury in the third quarter of the 49ers' 41-34 win over the New England Patriots on Sunday and was unable to finish the game. The 12-year veteran was scheduled to have an MRI on Monday.
Harbaugh expects his starting defensive tackle to play if at all possible.
"If it's humanly possible, The Cowboy [Smith] will be out there, ropin' and ridin'. "
Smith has been a huge part of the 49ers' vaunted defense this season, leading the team with 77 quarterback pressures, 52 quarterback hits and three sacks. The pressure he applies from the tackle position has played a big role in opening up alleys for linebacker Aldon Smith, who is tied for the NFL lead with 19.5 sacks.
If Smith is is unable to play, it is likely that Ricky Jean-Francois would start in his place.