Kick-off is at 17:15.
The Treviso player excelled in the Celtic League last term and replaces fellow Argentina-born Luciano Orquera, who drops to the bench having been the main flyhalf during Italy's strong Six Nations campaign in February and March when they beat France and Ireland.
Edoardo Gori continues at scrumhalf as he looks to make the spot his own in a mini-series also involving Samoa and Scotland.
Lock and former captain Marco Bortolami returns to the line-up after a year out following a shoulder injury.
Teams:
South Africa:
15 Willie le Roux, 14 Bryan Habana, 13 JJ Engelbrecht, 12 Jean de Villiers (captain), 11 Bjorn Basson, 10 Morné Steyn, 9 Jano Vermaak, 8 Pierre Spies, 7 Willem Alberts, 6 Francois Louw, 5 Juandré Kruger, 4 Eben Etzebeth, 3 Jannie du Plessis, 2 Adriaan Strauss, 1 Beast Mtawarira
Substitutes: 16 Chiliboy Ralepelle, 17 Trevor Nyakane, 18 Coenie Oosthuizen, 19 Flip van der Merwe, 20 Arno Botha, 21 Ruan Pienaar, 22 Pat Lambie, 23 Jan Serfontein
Italy:
15 Andrea Masi, 14 Giovanbattista Venditti, 13 Luca Morisi, 12 Alberto Sgarbi, 11 Luke Mclean, 10 Alberto Di Bernardo, 9 Edoardo Gori, 8 Sergio Parisse (captain), 7 Robert Barbieri, 6 Alessandro Zanni, 5 Marco Bortolami, 4 Antonio Pavanello, 3 Lorenzo Cittadini, 2 Leonardo Ghiraldini, 1 Alberto De Marchi
Substitutes: 16 Davide Giazzon, 17 Matias Aguero, 18 Martin Castrogiovanni, 19 Valerio Bernabo, 20 Joshua Furno, 21 Tobias Botes, 22 Luciano Orquera, 23 Tommaso Iannone