Jean de Villiers will make his return to top level rugby from the bench for the Springboks against the World XV in Cape Town on Saturday.
Victor Matfield will captain the Boks, with Warren Whiteley making his first start at eight, while two uncapped players, Jesse Kriel and Vincent Koch, have been included in the matchday 23.
If De Villiers makes an appearance it will be his first rugby since suffering a dislocated knee and ligament damage in the final match of 2014, against Wales in Cardiff.
De Villiers has gone through more than seven months of rigorous rehabilitation and is now completing a remarkable recovery.
"Jean is a massive asset to South African rugby and it’s wonderful to know his return to play is progressing so well that we can give him some game time from the bench on Saturday," said Springbok coach Heyneke Meyer.
"The mere fact that he is back in shape and ready to play is testament to his incredible work-ethic and his professional approach to the game. Jean has really put in hours and hours of extra work to get here and he is a great example for any player on how to put yourself in the best possible position to recover.
"We will still manage how he is used against the World XV and afterwards we’d like him to return to Western Province, where he will be available for their Absa Currie Cup warm-ups."
Meyer said of the selection of Whiteley, Kriel and Koch: "All three of them were magnificent in Vodacom Super Rugby and they deserve this opportunity. I’m excited to see how they step up to this level.
"I’ve always rated Vincent and followed his career for a long time. He has really improved a lot recently, which is testament to the hard work he and everyone who has worked with him, has put in. He has proved that players can become Springboks from one of the so-called smaller unions.
"Warren is a specialist number eight and will have big shoes to fill with Duane Vermeulen out injured. Although he has played in only two Tests, he brings experience and leadership to the pack, having led the Emirates Lions with great style this season.
"The reason we’ve decided to go with Francois Louw and Marcell Coetzee is because we have lost some ball-stealing ability with Duane not available, but both our flanks can now fulfil that role.
"Jesse has played at outside centre before and starred for the Junior Springboks in that position in four of their five matches in 2014. He’s also been training with us for a long time and I’m sure he will slot in easily with Damian de Allende in an exciting but a little inexperienced midfield combination.
"I’m very excited to see how Jesse, Damian and Handré Pollard will play next to each other. They are still young and I believe they are the future. They will also have a very experienced back-trio next to them on Saturday. It’s important to have a combination of youth and experience and we’ll continue to work on that."
Meyer also announced that following a meeting with Jaque Fourie on Tuesday, a mutual decision was taken that he would return to Kobe, his club in Japan, to regain his fitness and to get game time.
"He decided to withdraw from the Springbok squad for now, but we agreed that the door is still open for him to be selected for the Rugby World Cup if he is needed," said Meyer.
South Africa: 15 Willie le Roux, 14 JP Pietersen, 13 Jesse Kriel, 12 Damian de Allende, 11 Bryan Habana, 10 Handré Pollard, 9 Ruan Pienaar, 8 Warren Whiteley, 7 Marcell Coetzee, 6 Francois Louw, 5 Victor Matfield (c), 4 Eben Etzebeth, 3 Jannie du Plessis, 2 Bismarck du Plessis, 1 Tendai Mtawarira.
Replacements: 16 Adriaan Strauss, 17 Trevor Nyakane, 18 Vincent Koch, 19 Oupa Mohoje, 20 Schalk Burger, 21 Cobus Reinach, 22 Pat Lambie, 23 Jean de Villiers.
Date: Saturday, 11 September
Venue: Newlands, Cape Town
Kick-off: 17:00 local (15:00 GMT)
Referee: John Lacey (Ireland)
Assistant referees: Marius van der Westhuizen (South Africa), Jason Jaftha (South Africa)
Television match official: Deon van Blommestein (South Africa)