The tourists lost 22-17 in Durban last Saturday and Lancaster knows his side must now win in Johannesburg to stand any chance of victory in the three-Test series.
But the England boss insists he is approaching the match as he would any other.
Lancaster said: "Every game you play at international level, we want to win.
"Now we are in a three-game series and we've lost the first, so it's hugely important for us to get a win.
"But we tend to focus our efforts and energies on performance and trying to get the detail right.
"We've got to make sure we get our defensive system right, get our set-piece right - quality lineout ball and good scrum ball, and our attacking options in place.
"Our emphasis will be on focusing on the details of the performance rather than the outcome of the game at the end."
London Irish centre Jonathan Joseph will make his first start as England look to add a cutting edge to their backline. Toby Flood and David Strettle also come into the back division, with Ben Foden returning to full-back.
Flood replaces the benched Owen Farrell at fly-half, with Joseph coming in for the injured Brad Barritt and Manu Tuilagi will shuffle across to inside centre.
With Mike Brown injured, Foden will wear the No.15 jersey, allowing Strettle to return on the wing.
Lancaster has made two further changes on the bench, with Alex Corbisiero and Alex Goode coming into the squad. Leicester Tigers No.8 Thomas Waldrom has now also been called up to the bench after Phil Dowson was forced to withdraw from the squad.
South Africa have made just the one change to their line-up - with Pat Lambie recalled at full-back.
The Sharks ace comes into the starting XV after Zane Kirchener suffered a knee injury in the first Test victory.
Bjorn Basson will take Lambie's spot on the bench, with Werner Kruger also named among the replacements after Coenie Oosthuizen was ruled out for three months.
"We decided against no unnecessary changes as we aim to build some continuity during this season," explained coach Heyneke Meyer.
"This weekend will be a big challenge yet again against a good England side, but our focus is still on ourselves. We need to show further improvement from last weekend and have to make a step up this weekend.
"We have confidence in all the players in our squad and that is why Pat, Werner and Bjorn have slotted in easily. Everyone knows what is needed this weekend and they have been very sharp at training. We now need to translate that to the match on Saturday."
South Africa: 15 P Lambie; 14 JP Pietersen, 13 J de Villiers (capt), 12 F Steyn, 11 B Habana; 10 M Steyn, 9 F Hougaard; 1 T Mtawarira, 2 B du Plessis, 3 J du Plessis; 4 E Etzebeth, 5 J Kruger, 6 M Coetzee, 7 W Alberts, 8 P Spies.Replacements: 16 A Strauss, 17 W Kruger, 18 F van der Merwe, 19 K Daniel, 20 R Pienaar, 21 W Olivier, 22 B Basson.
England: 15 B Foden, 14 C Ashton, 13 J Joseph, 12 M Tuilagi, 11 D Strettle, 10 T Flood, 9 B Youngs, 1 J Marler, 2 D Hartley, 3 D Cole, 4 M Botha, 5 G Parling, 6 T Johnson, 7 C Robshaw, 8 B Morgan.Replacements: 16 L Mears, 17 A Corbisiero, 18 T Palmer, 19 T Waldrom, 20 L Dickson, 21 O Farrell, 22 A Goode.
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