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The Uruguay star was sent-off and Ghana awarded a penalty – missed by Asamoah Gyan.
The South Americans eked their way into the last-four on spot kicks in a cruel blow for Ghana, who would have become the first African side to ever reach a World Cup semi final.
Now they meet again, this time in the final round of group fixtures – and only one can progress to the knockout stage.
SunSport takes a look at everything you need to know ahead of the big game, including scoreline prediction.
How are they getting on?
Ghana: In a word: exciting.
They lost their group stage curtain-raiser 3-2 against table-topping Portugal, before winning their next 3-2 against South Korea.
Ghana showed great strength to eke out a win against Son Heung-min and Co having led 2-0, before being pegged back to 2-2, eventually snatching a winner.
Uruguay: Not well at all, by their standards.
They drew their opener against South Korea 0-0 before losing to Portugal 2-0.
Any injuries to worry about?
Ghana: Gideon Mensah insists he’s fit to start despite being taken off late in the 3-2 thriller against South Korea.
Uruguay: Ronald Araujo is yet to feature in this tournament and is unlikely to start.
But Luis Suarez could be given the nod, despite Darwin Nunez and Edinson Cavani being preferred against Portugal.
What’s at stake?
Ghana: It’s a slightly simpler route to the last 16 for Ghana.
If they win, they’re through.
A draw will be enough unless South Korea beat Portugal.
In that scenario, Ghana will need South Korea to win by no more than one goal, otherwise the Asian giants will beat them to the knockout stages.
Uruguay: It’s must-win time for the South Americans.
In fact, they need to grab all three points and hope South Korea don’t beat table-toppers Portugal.
If Uruguay and South Korea win, it’s all down to goal difference.
Uruguay trail South Korea by one, so would need to win their match by a bigger margin than their qualification rivals.
What’s the head-to-head?
These two nations have only ever met ONCE.. and it was that match in 2010.
Luis Suarez’s 120th-minute, goal-line handball saw him sent off and a penalty awarded.
But Asamoah Gyan missed it, as Uruguay made it into the World Cup semi-finals on spot-kicks, with Suarez calling his handball the “save of the tournament”.