Cast
Dwayne Johnson as Jack Bruno, who is a Las Vegas cab driver and a former convict. The director wrote in a cab driver as a main character because there was a unique relationship between the driver and his passengers. Fickman explained: "When Dwayne's driving and two aliens appear in his cab, he's stuck with them, there is an implied contract that I will get you to your destination, because that's what he does." This is Johnson's second Disney film, following the 2007 family comedy film The Game Plan, also directed by Andy Fickman.
AnnaSophia Robb as Sara, sister of Seth, a girl with telekinetic and telepathic powers. Fickman chose Robb based on her performance as Leslie Burke in Bridge to Terabithia. She is kind to Bruno and is the more compassionate of the two siblings. The only time she does not refer to Jack by his full name (Jack Bruno) is when she says goodbye to him, when she refers to him only as "Jack".
Alexander Ludwig as Seth, brother of Sara, a boy with the power to control his molecular density – "phasing" to become very dense, evidently giving him some degree of invulnerability, or become insubstantial and pass through solid objects. He is very cold to Bruno at first, not trusting him very much, but apologizes in the end saying that if it were not for him they would have not finished their mission. Both siblings talk using overly formal, emotionless, and analytical voices, and are always addressing Bruno by both his first and last name in all situations.
Carla Gugino as Dr. Alex Friedman, a discredited astrophysicist. Fired from her university, she is relegated to giving a lecture at a UFO conference about hard science. She becomes Jack's love interest. Fickman was a fan of Gugino's role in the short-lived television series Threshold.
Ciarán Hinds as Henry Burke, the leader of Project Moon Dust. Sarcastic and unscrupulous, he has no regard for morality, as demonstrated after Seth and Sara are imprisoned in Witch Mountain when he orders them to be experimented on so he can harness their powers, regardless of the possibility that they could die. As long as he gets results, whether they live or die does not matter to him. Hinds described his character as a man in black, explaining: "I'm the head of the operation who's contacted directly by a man you never see...[It] is about protecting the country. He's responsible for it, and he'll do whatever needs to be done. That's how he sees it."
Tom Woodruff Jr. as The Siphon, a well-trained alien assassin. Its full title "Siphon Warrior-series, Deranian 75" is a homage to the character Lucas Deranian (portrayed by Donald Pleasure) in the original 1975 film.
Garry Marshall as Dr. Donald Harlan, a friend of Alex's and author of UFO-related books, who thinks he can "tell when people are lying to me". He is seen tricking Burke into going after him by trading cars with Jack.
Tom Everett Scott as Mr. Matheson, a government agent working for Burke
Cheech Marin as Eddie Cortez, the auto mechanic who gets frustrated when people come to his shop in the middle of the night, when it is closed
Chris Marquette as Pope, one of Burke's agents
Eva Huang as Shira the UFO Huntress
Billy Brown as Mr. Carson
Dennis Hayden as Ray
William J. Birnes, the host of UFO Hunters, in a cameo
Whitley Strieber, author of Communion, in a cameo
Kim Richards and Ike Eisenmann, who portrayed Tia and Tony in the original Witch Mountain films of the 1970s, make cameos respectively as a roadhouse waitress named Tina (a minor change from Richards's character Tia in the 1975 and 1978 films) and as Sheriff Anthony (a reference to Eisenmann's character Tony from the previous films). Meredith Salenger, the star of Disney's 1985 adventure The Journey of Natty Gann makes a cameo as TV reporter Natalie Gann.
