The Serbian midfielder comes into the side as Jurgen Klopp makes seven changes following the 2-1 league win over Chelsea.
There is a debut for summer signing Loris Karius in goal, while Ragnar Klavan comes in at centre-back alongside Joel Matip.
The much maligned Alberto Moreno gets the chance to get his Anfield career back on track as he's handed a start at left-back with James Milner dropping to the bench.
Grujic comes into the midfield where he will have captain Jordan Henderson and Lucas Leiva for company.
Divock Origi leads the line with the fit again Roberto Firmino and Philippe Coutinho operating either side of him.
Former Liverpool player Tom Ince is on the bench for Derby but goalkeeper Scott Carson is not in the squad.
Liverpool: Karius, Clyne, Klavan, Matip, Moreno, Henderson, Lucas, Grujic, Firmino, Coutinho, Origi.
Subs: Mignolet, Lovren, Milner, Can, Ejaria, Mane, Ings.
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