- The film is the first live-action film by Oscar-level animation director Brad Bird.
- Tom Cruise and Vin Reims are the only two actors in the film who have participated in all four "Mission Impossible" movies.
- The character of Brandt was once designed as a replacement for Ethan Hunt. Because for a while, Tom Cruise was tired of playing this super agent on the screen again. The producer had to redesign a character to replace Ethan Hunt to continue the campaign. But in the end Cruise decided to play Ethan again.
- Anthony McKay, Christopher Aigan, Kevin Siggs, Chris Pine and Tom Hardy were all once candidates to play Brandt. This role was eventually handed over to Jeremy Renner.
- Jessida Barrett once came to the crew to audition.
- At the end of a trailer of the film, a missile can be seen flying over San Francisco and hitting the enemy's command center. In fact, it flew to the headquarters of Pixar.
Mission: Impossible - Ghost Protocol behind the scenes gags
Mission: Impossible - Ghost Protocol quotes
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Benji Dunn: I'd be more worried about the heat.
William Brandt: [pauses] And then there's that. What heat?
Benji Dunn: Well it's just like any other computer. If you switch the fan off it's gonna get pretty hot in there.
William Brandt: Heh. Of course.
Benji Dunn: Relatively.
William Brandt: So I'm jumping into a... an oven, essentially.
Benji Dunn: Yeah, essentially. But, uh, I catch you.
William Brandt: Great.
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Jane Carter: [Telling Ethan about agent Hanaway, who was killed by a female assassin in the course of Carter's field op] It was my op. I put him in the field. And she left him just alive enough for me to see him die.