Second-rower Schofield, who joined the Warriors from Top 14 outfit Toulon in the summer, is one of four changes to the starting XV that edged out 22-21 on home soil last week.
Errie Claassens is gets the nod at full-back, Jon Clarke comes into the centres to partner Alex Grove in midfield, while Andy Short is named on the wing for the clash.
There are also four changes on the bench with returns for prop George Porter and lock Gillies in the forwards and Ben Howard and Danny Gray in the three-quarters.
Worcester head coach Richard Hill is hoping his side can continue their recent form, stating: "The players are on a roll at the moment. We have momentum and that is crucial for us.
"There is no reason after the hard work of beating Perpignan at Sixways to go to France with half a team. We are going full out and we want to get into the quarter finals of the Amlin Challenge Cup."
Perpignan have made three changes to the side that were pipped at Sixways last weekend with former Wasps and Saracens full-back Richard Haughton taking over in the No. 15 shirt from Joffrey Michel.
Elsewhere, Tongan Lifemi Mafi is selected in the centres alongside compatriot Sione Piukala, while Betrand Guiry is preferred at openside flanker to Luke Narraway who drops to the bench.
Worcester: 15 Errie Claassens, 14 Nikki Walker, 13 Alex Grove, 12 Jon Clarke, 11 Andy Short, 10 Andy Goode, 9 Paul Hodgson; 1 Ceri Jones, 2 Ed Shervington, 3 Euan Murray, 4 Dean Schofield, 5 Chris Jones, 6 Neil Best, 7 Matt Kvesic, 8 Semisi Taulava.
Replacements: 16 Aleki Lutui, 17 George Porter, 18 John Andress, 19 Craig Gillies, 20 Sam Betty, 21 Jonny Arr, 22 Danny Gray.
Perpignan: 15 Richard Haughton, 14 Farid Sid, 13 Lifemi Mafi, 12 Sione Piukala, 11 Adrien Plante, 10 James Hook, 9 Florian Cazenave, 8 Henry Tuilagi, 7 Betrand Guiry, 6 Alasdair Strokosch, 5 Romain Taofifenua, 4 Sebastien Vahaamahina, 3 Nicolas Mas, 2 Guilhem Guirado, 1 Sona Taumalolo.
Replacements: 16 Romain Terrain, 17 Jerome Schuster, 18 Kisi Pulu, 19 Robins Tchale Watchou, 20 Luke Narraway, 21 David Mele, 22 David Marty, 23 Gavin Hume.
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