Matt Cox starts at number eight in place of GJ van Velze, who has a shoulder injury, while Pierce Phillips partners Anton Bresler at lock.
Wing Cadan Murley makes his Premiership debut for Harlequins after impressing in the Premiership Rugby Cup.
Joe Marler and Max Crumpton return to the front row and co-captain James Horwill is on the bench after injury.
Worcesters return to Premiership action after a five-week break did not go well last weekend as they were beaten 28-13 at Bath.
Warriors had won twice in three league games prior to that – and have won their last six matches at Sixways in all competitions.
But they have lost on their last two visits to Worcester; 24-17 in 2017 and then 44-13 in April, the day the hosts secured Premiership safety.
Worcester: Pennell; Heem, Venter, Mills (capt), Humphreys; Weir, Hougaard; Black, Singleton, Schonert, Bresler, Phillips, Hill, Lewis, Cox.
Harlequins: Brown; Murley, Marchant, Tapuai, Earle; Smith, Mulchrone; Marler, Crumpton, Collier, Merrick, Symons, Dombrandt, Clifford, Chisholm (capt).
CROCKED captain Gerrit-Jan van Velze has been ruled out of Worcester Warriors’ Gallagher Premiership clash with Harlequins at Sixways on Friday night (7.45pm).
The club have confirmed van Velze has sustained a shoulder joint injury, meaning centre Ryan Mills will skipper the side who have made three changes to the starting line-up.
Matt Cox who came off the bench in last weekend’s 28-13 defeat at Bath will start at number eight in place of van Velze.
Sam Lewis retains his place at openside flanker while the returning Ted Hill replaces Matti Williams at blindside.