A surgical stapling instrument comprising a tissue cutting knife movable through a staple cartridge to perform a staple firing stroke is disclosed. The stapling instrument further comprises a lockout system configured to prevent the tissue cutting knife from being moved through the staple firing stroke if the staple cartridge is missing from the stapling instrument and/or if the staple cartridge has been previously fired. The lockout system comprises a flexible spring that acts on the bottom of the tissue cutting knife at the initiation of the staple firing stroke to push the tissue cutting knife into a lockout recess if the staple cartridge is missing or has been previously fired.