Second-year pro Michael Wilhoite is Willis’ top backup.
Willis suffered the groin injury in San Francisco’s Week Three loss to Indianapolis.
The 49ers will also be without reserve cornerback Nnamdi Asomugha (knee). The Niners’ other inactives are linebacker Jermaine Cunningham, wide receiver Chris Harper, offensive guard Joe Looney, wide receiver Quinton Patton and quarterback John Skelton.
The Texans’ inactives, per the club, are offensive guard Brandon Brooks, inside linebacker Tim Dobbins, offensive tackle Andrew Gardner, defensive end Tim Jamison, wide receiver Lestar Jean, quarterback Case Keenum and defensive end Sam Montgomery.