Giant-killing or giant killer may refer to:
- Killing a literal giant, such as:
- Gigantomachy, a Greek mythological battle
- David and Goliath, a biblical story
- "Jack the Giant Killer", a Cornish fairy tale and legend
- Upset (competition), occurring when an underdog beats the favourite (or top dog)
- Underdog, a person or group in a competition who is largely expected to lose
- Giant Killing, a Japanese manga and anime series
- Giant Killer (call sign), an American military aviation call sign
- "Giant Killer" (story), a 1945 short story by A. Bertram Chandler
- Giantkiller, a DC Comics limited series