Giant Killers or Giant Killer may refer to:

Air traffic control

• Giant Killer (call sign), used in the United States

Entertainment

• Giantkiller, a comic book series
• "Giant Killer" (story), a 1945 sci-fi short story by A. Bertram Chandler
• Giant Killers (video game), a 2001 football-management simulator video game
• Giant Killers (band), a 1994 performer on Top of the Pops
• Giant Killers (EP), a 2017 release by Japanese idol group BiSH
• The Giant Killer the UK title for the 2013 film Jack the Giant Killer, starring Ben Cross

Sports

• Giant killers (sports), an underdog team or person that defeats an expected winner
  • 1967 Oregon State Beavers football team, nicknamed "Giant Killers" for their performance