The clash will see two former African champions battle it out for top spot in Group E.
Bafana Bafana have the home ground advantage as the match is scheduled to take place at the FNB Stadium in Johannesburg.
The 1996 Afcon champions will also be spurred by the fact that they defeated the Super Eagles in the last meeting between the two teams which was played in Uyo.
Goals from Percy Tau and Tokelo Rantie secured South Africa's first competitive win over Nigeria.
However, since then, the Super Eagles have been on the rise in their qualifying campaign - recording three consecutive victories which took the them to the summit of the standings.
Bafana on the other hand, have blown hot and cold in their qualifying campaign since their memorable victory on match-day one.
Although the Southern African giants are the only undefeated side in Group E, the two draws against Libya and Seychelles slightly dented their hopes of qualifying for the showpiece.
They are currently placed second on the standings - one point behind Nigeria, while third-placed Libya still have a chance of qualifying for the finals provided they win their remaining two matches and Bafana stumble.
PRESSURE & HISTORY
The group winner and runners-up will qualify and the three teams which are still in contention know that they cannot afford to slip up in the last two matches.
The pressure will be on Bafana, who need to secure a win over Nigeria in order to book their place in the finals.
Pressure tends to get to Stuart Baxter's side as they dropped two crucial points against Libya when they were expected to win at home in Durban two months ago.
The four-time Cosafa Cup winners delivered an uninspired performance resulting in a 0-0 draw with the Mediterranean Knights in front of their own supporters at the Moses Mabhida Stadium.
A draw between Bafana and Super Eagles will see the latter qualify, and South Africa would then need a favour from Group E's whipping boys, the Pirates of Seychelles, who are set to host Libya on Saturday.
The Mediterranean Knights are strong favourites to beat Seychelles, who have conceded a whopping 14 goals in their qualifying campaign which simply means Bafana cannot rely on the Pirates to do them a favour.
History also favours the West African giants as they have never lost to South Africa away from home in a competitive match and they will look to keep that record intact.
The two teams drew 0-0 in their last competitive meeting in South Africa four years ago which was the 2015 Afcon qualifier at the Cape Town Stadium.
But overall, Nigeria have the upper hand because they have won seven of their previous 13 matches against Bafana and lost just two, while the other four matches ended in draws.
Also, they are familiar with the territory in Johannesburg as this is the same venue where they lifted the 2013 Afcon trophy.