The home side need just a point to confirm their place as winners of Group G, while the visitors have to come away with all three to stand any chance of avoiding finishing bottom of the group.
Match preview
Mali saw off the threat of Congo thanks to a 2-0 victory over Congo when the teams locked horns at Stade Alphonse Massemba-Debat on June 18.
Off the back of a relatively uneventful first period, second-half goals from Ibrahima Kone and Dorgeles Nene got the job done for Eric Chelle's men.
Consequently, Les Aigles sit top of their qualifying group with 12 points from five matches, three points clear of nearest challengers Gambia.
Awaiting them next is the challenge of an opposing outfit who have been beaten in each of the previous five encounters between the teams.
Currently on a run of five wins and three stalemates from their last eight home matches, Friday's hosts are huge favourites to come out on top in this one.
South Sudan fell to a comprehensive 3-0 defeat against the Pharaohs of Egypt in a friendly matchup at the Cairo International Stadium on June 18.
Mostafa Fathi and Kahraba netted in the first half to leave Stefano Cusin's men before Trezeguet put the result beyond doubt 18 minutes from time.
That was a fourth defeat in five matches for the Bright Stars who remain rooted to the foot of their qualifying group having only picked up three points from five games.
Having kept just one clean sheet in 10 matches on the road leading up to Friday's visitors will need to keep things at the back in their quest to avoid another fruitless outing away from home.
Mali Africa Cup of Nations Qualifying form:
W
L
W
Mali form (all competitions):
D
D
L
W
L
W
South Sudan Africa Cup of Nations Qualifying form:
W
L
L
South Sudan form (all competitions):
W
L
L
L
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Team News
El Bilal Toure is unavailable for Mali as he continues to nurse a thigh injury he sustained in Atalanta's final pre-season friendly against Juventus.
Having scored twice in three games this season, forward Sekou Koita is the favourite to replace Toure in the hosts' starting lineup for this one.
Despite only making his debut in 2020, Tito Okello currently sits joint-second in South Sudan's all-time scoring charts and will be looking to deliver the goods once again.
Khamis Daniel's was in goal for the away side against Egypt but his involvement between the sticks here remains uncertain as the goalkeeper is currently without a club.
Mali possible starting lineup:
Diawara; Dante, Fofana, Kouyate, Traore; Camara, Samassekou, Bissouma, Haidara; Coulibaly, Koita
South Sudan possible starting lineup:
John; Achol, Atendele, Dhata, Loki; Malish, Manyang, Toha; Chol, Yuel, Okello