The DJ group's latest track 'Don't You Worry Child' is currently leading the tally by 22,000 copies, while Adele's James Bond theme 'Skyfall' trails at two.
Rihanna's 'Diamonds' slides to three, 'Gangnam Style' by Psy is at four and Leona Lewis is a new entry at five with 'Trouble'.
Elsewhere, Maroon 5's 'One More Night' lands at 26, while Disclosure look set to make their Top 40 debut with 'Latch', which is currently at number 39.
Eliminated X Factor contestant Carolynne Poole has had an effect on the chart with her sing-off performance of Faith Hill's 'There You'll Be' at 36 and Nicki Minaj's 'Starships' up to 37.
Over on the album chart, Ellie Goulding is on course to claim her second number one album in the UK with Halcyon.
Mumford & Sons remain at two with Babel, while Muse slip to three with The 2nd Law.
All Time Low land at four with Don't Panic, Jeff Lynne is at five with Long Wave and Kiss are at 12 with their 20th studio collection Monster.
Mika's The Origin Of Love looks set for a number 15 debut, while Lemar's fifth studio album Invincible is at 39.
Watch the music video for Swedish House Mafia's 'Don't You Worry Child' below: