Venter, who won his sole Springbok cap last season, will feature in the second row rather than his usual position on the blindside flank.
In the backline, exciting young scrumhalf Nico Steyn steps in to replace the injured Morne van den Berg, with rookie Layton Horn named as his backup.
With Francke Horn unavailable, experienced hooker Jaco Visagie will once again captain the team from the front row.
Van Rooyen has kept faith with the midfield duo of Bronson Mills and Henco van Wyk, while Kade Wolhuter retains the number 10 jersey.
Lions: 15 Quan Horn, 14 Richard Kriel, 13 Henco van Wyk, 12 Bronson Mills, 11 Edwill van der Merwe, 10 Kade Wolhuter, 9 Nico Steyn, 8 Jarod Cairns, 7 Renzo du Plessis, 6 JC Pretorius, 5 Ruan Delport, 4 Ruan Venter, 3 Asenathi Ntlabakanye, 2 Jaco Visagie (captain), 1 Morgan Naude.
Replacements: 16 PJ Botha, 17 SJ Kotze, 18 RF Schoeman, 19 Darrien Landsberg, 20 Sibabalo Qoma, 21 Layton Horn, 22 Lubabalo Dobela, 23 Rynhardt Jonker.