 | Emmanuelle Vaugier als Jane Browning / Painkiller Jane |
 | Eric Dane als Nick |
 | Richard Roundtree als Colonel Watts |
 | Venus Terzo als Carla Browning |
 | Walker Howard als Blue |
 | Callum Keith Rennie als Mitchell |
 | Tate Donovan als Dr. Graham Knight / Lucas Insley |
 | Paula Brancati als Young Jane |
| Elicia Mackenzie als Young Carla |
 | Martin Cummins als Sergeant Flynn |
 | Richard Harmon als Squeak |
| Brian Tyler | Music |
| John Harrison | Writer |
| Richard Hudolin | Production Design |
| Stephen McNutt | Director of Photography |
| Lisa Love | Makeup Artist |
| Dominique Fauquet-Lemaitre | Set Decoration |
| Don Keith Opper | Writer |
| Marny Eng | Stunts |
| Melissa R. Stubbs | Stunt Coordinator |
| Lauro Chartrand | Stunt Coordinator |
| Harvey Frand | Producer |
| Andrew Seklir | Editor |
| Sanford Bookstaver | Director |
| Jenni Gullett | Costume Design |
| Pearl Louie | Makeup Department Head |
| Diane Widas | Costume Design |
| Doug McLean | Art Direction |
