Jennifer Lopez as Terri Flores - She is the documentary director who leads a crew to look for the long-lost indigenous tribe called the Shirishamas on the Amazon Rainforest. Terri is a sedulous courageous woman, who is committed to her profession and mindful of her crew.
Ice Cube as Danny Rich - He is the cameraman and a childhood friend of Terri Flores. He is a brave man who looks after the welfare of his friends and protects them from any danger.
Jon Voight as Paul Serone - He is a deserted Paraguayan snake hunter. He makes Terri’s crew believe that he knows the way to the tribe they are looking for. They are not aware of Serone’s true intention which is to hunt down and capture a giant record-breaking green snake, anaconda, whom he has been searching for for years.
Eric Stoltz as Dr. Steven Cale - He is an anthropologist who gets stung by a wasp in the throat which leaves him benumbed for a long time. He is among the few survivors who face the anaconda and gives his best to safeguard his confidants.