Yaqeen Ahmed, Sebastian de Klerk, Luan Giliomee, Markus Muller, Riley Norton and Emmanuel Tshituka have yet to earn a test cap but all six have been involved in the Springboks set-up before.
Ahmed, Giliomee, Muller and Tshituka represented the South Africa 'A' team against Zimbabwe in June, while Norton played for the Springboks against the Barbarians the same month. De Klerk attended a Springboks training camp last season.
Veteran stars Cheslin Kolbe, Eben Etzebeth, Andre Esterhuizen and Handre Pollard have been ruled out because of injury.
South Africa play away against Italy, France and Ireland before the finals weekend at Twickenham at the end of November.
South Africa lead the Southern Hemisphere standings on points difference ahead of New Zealand, with both teams on 15 points.
South Africa squad:-
Backs: Yaqeen Ahmed (Stormers), Kurt-Lee Arendse (Mitsubishi Dynaboars), Damian de Allende (Wild Knights), Sebastian de Klerk (Bulls), Aphelele Fassi (Sharks), Sacha Feinberg-Mngomezulu (Stormers), Luan Giliomee (Bulls), Ethan Hooker (Sharks), Jesse Kriel (Canon Eagles), Manie Libbok (Kintetsu Liners), Canan Moodie (Bulls), Markus Muller, Cobus Reinach (both Stormers), Morne van den Berg (Lions), Edwill van der Merwe (Sharks), Damian Willemse (Stormers), Grant Williams (Kobe Steelers).
Forwards: Lood de Jager (Wild Knights), Paul de Villiers (Stormers), Pieter-Steph du Toit (Toyota Verblitz), Thomas du Toit (Sharks), Cameron Hanekom (Bulls), Siya Kolisi, Wilco Louw (both Stormers), Malcolm Marx (Kubota Spears), Ntuthuko Mchunu (Stormers), Salmaan Moerat (Stade Rochelais), Franco Mostert (Honda Heat), Ox Nche (Sharks), Ruan Nortje (Kubota Spears), Riley Norton, Zachary Porthen (both Stormers), Gerhard Steenekamp (Bulls), Emmanuel Tshituka (Sharks), Marco van Staden, Jan-Hendrik Wessels (both Bulls), Jasper Wiese (Urayasu D-Rocks).
