Dubuisson, who has not won since lifting the Turkish Airlines Open for the second time in 2015, was in good form for the second day running and was just one of 11 players to shoot under-par on Friday.
The Frenchman, who had to leave the course for a period of time with three holes to play due to a thunderstorm, made four birdies and two bogeys for a two-under-par round of 70, leaving him alone at the top on six-under.
It could have been better for the 27-year-old had he not dropped a shot on the final hole but he will be happy to take a two-stroke advantage going into the weekend's play in Sun City.
England's Lee Westwood and South African Darren Fichardt carded rounds of 70 and 69 respectively to leave the pair in a share of second on four-under, whilst defending champion Alex Noren heads a group of four players a shot further back.
The Swede, who signed for a level-par 72, is joined by Scotland's Scott Jamieson and the English pair of Ross Fisher, who still has a chance of winning the Race to Dubai, and Tyrrell Hatton.
German Martin Kaymer and South African Charl Schwartzel, who bogeyed 17 and 18, are a stroke further back on -2 and the duo will be hoping for a fast start on Saturday to put the pressure on those above them.