- Sam Worthington as Jake Sully, "a paralyzed former marine who undergoes an experiment to exist as an avatar, another version of himself... an alien – 10 feet (three meters) tall and blue." Sully is able to be part of the alien world in his avatar, a genetically engineered biological body that can be remotely operated by a human consciousness. Director James Cameron cast the Australian actor after searching the world for promising young actors, preferring relative unknowns to keep the budget down. Worthington auditioned twice early in development, and he has signed on for possible sequels.
- Zoë Saldaña as an alien Jake initially betrays, but they both fall in love. The character will be entirely computer generated. Saldaña has also signed on for sequels.
- Sigourney Weaver as Grace, a botanist who mentors Jake Sully. Weaver dyed her hair red for the part.[11] Her character was named Shipley at one point. The character reminded Weaver of Cameron himself, being "very driven and very idealistic".
- Michelle Rodriguez as an ex-marine pilot. Cameron had desired to work with Rodriguez since he had seen her in Girlfight (2000).
- Giovanni Ribisi as Selfridge, a passive-aggressive character.
- Stephen Lang as a Marine Corps colonel. Lang had auditioned for a role in Cameron's Aliens (1986) that he did not get, but the director remembered Lang and cast him into Avatar.
- Joel David Moore as an anthropologist who studies plant and nature life like Weaver's character.
- Matt Gerald as the main villain.
Actors Wes Studi, C.C.H. Pounder, Laz Alonso, and Peter Mensah are also in the film. Actor Michael Biehn entered talks with Cameron in March 2007 for a possible role in the film, but his involvement is not confirmed.
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