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- Sam Worthington as Jake Sully
- Zoe Saldana as Neytiri
- Stephen Lang as Colonel Miles Quaritch
- Sigourney Weaver as Dr. Grace Augustine
- Michelle Rodriguez as Trudy Chacon
- Giovanni Ribisi as Parker Selfridge
- Joel David Moore as Dr. Norm Spellman
- C.C.H. Pounder as Mo'at
- Dileep Rao as Dr. Max Patel
- Wes Studi as Eytukan
- Laz Alonso as Tsu'tey
- Matt Gerald as Corporal Lyle Wainfleet