Cape Verde, with a population of just over half a million and a small playing pool to call upon, have confounded all expectations to claim a place among the last eight in their debut appearance at the finals.
The islanders take on Ghana in the day's other match at the start of the knockout phase of the tournament.
A dramatic win over Angola in their final group game, following two draws, made the islanders the toast of world soccer.
Cape Verde have suddenly gone from newcomers seeking to avoid humiliation to a team who believe they can now reach the semi-finals.
"We are a serious team and we have grown in confidence since the tournament started. We are stronger," said coach Lucio Antunes.
Ghana will have Mubarak Wakaso, who scored the only goal when they beat Cape Verde in a friendly in Portugal in November, back from suspension for the match in Port Elizabeth.
The tie is followed by the meeting in Durban of the home nation and Mali who finished third in last year's edition.
"To play the hosts with their crowd behind them in a wonderful stadium is a prestigious occasion we are looking forward to," said coach Patrice Carteron.