The rapper will replace Duran Duran, who were due to headline but have been forced to cancel due to singer Simon Le Bon's illness.
6,000 people are expected at the event, which will see the hip-hop artist supported by a DJ set from Mark Ronson, who also headlined the club last month.
Snoop Dogg played the event last month, with Primal Scream set to perform a live show of their Screamadelica album as the closing party on September 2.
50 Cent unveiled his new single 'I'm On It' last week. He recently cancelled the release of new album Black Magic after his ongoing dispute with record label Interscope.
Listen to 50 Cent's 'I'm On It' below: