The 22-year-old Pat Lambie starts at out-half in place of the injured Johan Goosen, while JP Pietersen returns on the right wing and Juandré Kruger comes into the second row.
The latter pair replace Bryan Habana and Andries Bekker respectively, who were both ruled out of the tour because of injury.
South Africa head coach Heyneke Meyer said: "I'm excited to see what Pat can bring to the team. He played very well in the last few weeks of the Currie Cup and hopefully he can bring that momentum with him on Saturday.
"It's also good to have JP back. He's had a great season and will want to finish the season on a high. At lock, there has been strong competition for the number 5 jersey all season and now Juandré gets an opportunity again."
The South African side is captained by former Munster centre Jean de Villiers. Ulster half-back Ruan Pienaar will wear the number 9 jersey with ex-Leinster prop CJ van der Linde, named on the bench, set for his first appearance since the 2011 Rugby World Cup.
"I've said from the outset that I'd like to see which of the players can handle the northern Hemisphere conditions on this tour, as it will be the same for the Rugby World Cup in 2015," explained Meyer.
"We'll be facing an Ireland team that is never an easy opponent in Dublin. The Springboks have only won one of their last four Tests here and since they lost at the Aviva Stadium against South Africa in November 2010, they have recorded a number of good victories at their home ground.
"They are a quality and well-balanced side with good experienced players. We've seen in our last number of Tests against Ireland how dangerous they can be, but we'd rather focus on our own game and would like to start this tour on a positive note."
Meyer also confirmed that Leinster prop Heinke van der Merwe has been called up to the South Africa squad for the duration of their tour. He played in his only Test for South Africa against Wales in November 2007, and he toured with the Springboks at the end of the 2009 season.
Gurthrö Steenkamp, who joined the squad on Tuesday evening, is struggling with a niggle, so van der Merwe's call-up provides extra cover at loosehead prop.
"Heinke has played for South Africa before and is based in Dublin, making it easy for him to join the squad. I've been following his career and he has been playing well for Leinster, who are the Heineken Cup champions," added Meyer.
SOUTH AFRICA Team & Replacements (v Ireland, 2012 GUINNESS Series, Aviva Stadium, Saturday, November 10, kick-off 5.30pm):
16 - Schalk Brits (Saracens)
17 - CJ van der Linde (Golden Lions)
18 - Pat Cilliers (Golden Lions)
19 - Flip van der Merwe (Blue Bulls)
20 - Marcell Coetzee (Sharks)
21 - Morné Steyn (Blue Bulls)
22 - Juan de Jongh (Western Province)
23 - Lwazi Mvovo (Sharks)