Tupou suffered a concussion in Japan's win over Scotland at Yokohama last weekend and drops out of the matchday 23 altogether, with livewire winger Lomano Lava Lemeki named among the replacements as cover for the back three.
Coach Jamie Joseph also made two changes to the forwards on the bench with Wimpie van der Walt and Amanaki Lelei Mafi replacing fellow big men Uwe Helu and Hendrik Tui for what is likely to be a physical battle against the Springboks.
Loosehead prop Jiwon Koo was forced off the pitch against the Scots by a rib injury but has recovered sufficiently to take his place in the front row.
Team: 15-Ryohei Yamanaka, 14-Kotaro Matsushima, 13-Timothy Lafaele, 12-Ryoto Nakamura, 11-Kenki Fukuoka, 10-Yu Tamura, 9-Yutaka Nagare, 8-Kazuki Himeno, 7-Pieter Labuschagne, 6-Michael Leitch (captain), 5-James Moore, 4-Luke Thompson, 3-Jiwon Koo, 2-Shota Horie, 1-Keita Inagaki
Replacements: 16-Atsushi Sakate, 17-Isileli Nakajima, 18-Asaeli Ai Valu, 19-Wimpie van der Walt, 20-Amanaki Lelei Mafi, 21-Fumiaki Tanaka 22-Rikiya Matsuda, 23-Lomano Lava Lemeki