The 'When You Were Young' band will top the bill on the Friday night of the festival on June 24, their first show in Europe since they went on hiatus in January 2010.
Drummer Ronnie Vannucci said: "It's been too long, friends. Feels like forever since we've seen each other and now it's time we pay a visit. "Have to get the machine oiled and ready to make this kinda thing happen more often. Feeling creative, let's do this."
Other acts who have been announced to play at Hard Rock Calling, which takes place in Hyde Park, London, include Adam Ant - who has recently launched his musical comeback - Rumer, Mike and the Mechanics, Barenaked Ladies, Lighthouse Family and Train.
Despite going on hiatus, The Killers appeared on the White House South Lawn on July 4, 2010 for the second annual "Salute To The Military" United Service Organizations concert after they had been invited by President Barack Obama, and at a campaign rally in July, as well as releasing a Christmas single in the US.
The group's break ended earlier this month, when they played the inaugural Lollapalooza festival to be held in Santiago, Chile.