Nigeria’s pedigree in this tournament makes them perennial contenders – victory would give them a sixth successive slot in the semi-finals and enhance their current run of three wins from their last four.
The three-time winners lifted the trophy in South Africa in 2013 and have lost just one of their last 11 matches – that setback against Madagascar in their final group game when coach Gernot Rohr rested several players.
Three goals by players with plenty of Premier League experience helped them knock out reigning champions Cameroon during a frenetic round-of-16 clash in which the Super Eagles showed their ruthlessness in response to having far less possession than the holders.
Former Watford striker Odion Ighalo put Nigeria ahead in Alexandria, only for Stephane Bahoken and Clinton Njie to turn the tables at half-time by both scoring within three minutes.
Nigeria will receive a significant boost should John Obi Mikel return from an injury that forced him to limp out of the defeat to Madagascar.
Rohr is understandably eager to involve the former Chelsea midfielder again and told reporters that he has been tentatively running in a bid to be ready for the quarter-final.
Now at Trabzonspor, Mikel has suggested he will not hurry his recovery and is certain of making a potential semi-final should he fail to be ready for the match with South Africa.
As well as helping Nigeria finish third at the 2006 and 2010 Nations Cups, Mikel was part of the 2013 AFCON-winning squad and appeared at the last two World Cups – and his experience has been key for the younger members of Nigeria’s squad this year.
Mikel, who took part in a light training session on Sunday, could be restored as captain, while there is likely to be further good news on the fitness of Jamilu Collins.
The Paderborn defender was confirmed fit and ready ahead of the last 16 fixture against the Indomitable Lions of Cameroon but sat out of the game.
Levante forward who has been tremendous in both defense and attack for the Eagles in the absence of right back Shehu, Moses Simon is likely to make way for Villarreal sensation Chukwueze as part of a Nigeria attack that could test South Africa’s flawless run of first-half clean sheets in their campaign so far.
Ighalo is the tournament’s joint top scorer with three goals, and his ratio of 93 minutes per goal means he has been narrowly less prolific than Senegal and Liverpool rival Sadio Mane.
Nigeria possible starting lineup:
Akpeyi; Ola Aina, Troost-Ekong, Omeruo, Collins; Ndidi, Etebo; Iwobi, Chukwueze, Musa; Ighalo