Two World Cup outsiders do battle in Johannesburg.
Uruguay coach Oscar Tabarez has confirmed that Mauricio Victorino will replace centre-back Diego Godin, who picked up a thigh injury against South Korea.
Tabarez named his starting line-up on Wednesday, with Alvaro Fernandez coming in for Alvaro Perreira in midfield.
Ghana midfielder Kevin-Prince Boateng is expected to recover from a hamstring injury in time to face Uruguay. Striker Asamoah Gyan is also likely to start despite hurting his ankle against the USA.
Fit-again defender Isaac Vorsah is set to replace the suspended Jonathan Mensah, while Sulley Muntari is tipped to come in for Andre Ayew, who serves a one-game ban.
One booking from suspension: Fucile, Lugano, Victorino (Uruguay); Addy, Annan, Tagoe (Ghana). (BBC Sport)
Uruguay take on the sole remaining African representative, Ghana, in what should be an evenly matched tie in Johannesburg.
Highlights of previous World Cup 2010 matches these two teams have taken part in.
Uruguay 2-1 South Korea
Ghana 1-1 Australia