The track, which is included on the group's debut album Hot Fuss, beat off competition from Arctic Monkeys' 'I Bet That You Look Good On The Dancefloor' at two and Kings Of Leon's 'Sex On Fire' in third place.
The Killers scored a second entry in the top ten with 'Somebody Told Me' at nine, while 'All These Things That I've Done' made 22 and 'When You Were Young' was voted in at 41.
Elsewhere, Franz Ferdinand's second single 'Take Me Out' made it to number 12 and Coldplay's 'Yellow' was voted 17th best song of the decade.
The top ten XFM songs of the decade:
1. The Killers: 'Mr Brightside'
2. Arctic Monkeys: 'I Bet That You Look Good On The Dancefloor'
3. Kings Of Leon: 'Sex On Fire'
4. Muse: 'Knights Of Cydonia'
5. Elbow: 'One Day Like This'
6. The White Stripes: 'Seven Nation Army'
7. Ian Brown: 'F.E.A.R.'
8. The Strokes: 'Last Nite'
9. The Killers: 'Somebody Told Me'
10. MGMT: 'Kids'