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- Thomas Jane as The Punisher
- John Travolta as Howard Saint
- Roy Scheider as Frank Castle, Sr.
- Will Patton as Quentin Glass
- Rebecca Romijn as Joan
- Laura Harring as Livia Saint
- Ben Foster as Spacker Dave
- John Pinette as Bumpo
- Samantha Mathis as Maria Elizabeth Castle
- Marcus Johns as Will Castle
- Russell Andrews as Agent James "Jimmy" Weeks
- James Carpinello as Robert "Bobby" Saint and John Saint
- Eddie Jemison as Mickey Duka
- Eduardo Yanez as Mike Toro
- Omar Avila as Joe Toro
- Kevin Nash as The Russian
- Mark Collie as Harry Heck
- Veryl Jones as Candelaria
- Tom Nowicki as Lincoln
- Hank Stone as Cutter