Gloucester Rugby prop Nick Wood and Sale Sharks lock Dean Schofield are also in the starting XV for the game that kicks-off at 2pm.
Fly-half Jonny Wilkinson and centre Andy Farrell also return to the starting line-up, while Peter Richards gets the nod at scrum-half.
Players from Wasps, Leicester and Bath did not travel to South Africa after coach Ashton decided that their participation in last weekend's Heineken Cup and European Challenge Cup finals ruled them out of contention.
Sanderson is joined on the bench by Saracens hooker Matt Cairns, along with Bristol veterans Darren Crompton and Roy Winters and Harlequins scrum-half Andy Gomarsall.
England Team to face South Africa: M Brown (Harlequins); D Strettle (Harlequins), M Tait (Newcastle), A Farrell (Saracens), J Robinson (Sale Sharks, capt); J Wlkinson (Newcastle), P Richards (Gloucester); N Wood (Gloucester), M Regan (Bristol) S Turner (Sale), D Schofield (Sale), A Brown (Gloucester), C Jones (Sale), A Hazell (Gloucester), N Easter (Harlequins).
Replacements: M Cairns (Saracens), D Crompton (Bristol), R Winters (Bristol), P Sanderson (Worcester), A Gomarsall (Harlequins), T Flood (Newcastle), I Balshaw (Gloucester).