Joe Marler returns from England's Six Nations camp to start for Harlequins in one of five changes to face Newcastle.
Wilco Louw, Sam Riley, Tommy Allan and Louis Lynagh also come back in.
Newcastle make four changes to the side which lost to Bath in their previous match for the trip to London.
Tom Marshall makes his first Premiership start at number eight, with flanker Sean Robinson, centre Pete Lucock and lock Rob Farrar also coming into the starting side.
Third-placed Quins have won 16 of their last 17 matches at home against Newcastle and won three of their last five league matches.
Newcastle, down in 11th place, have lost their last six Premiership matches and have the lowest tally of tries in the league.
Marler slots back into the front row having featured off the bench in all three of England's Six Nations matches so far. It will be the first time he and fellow prop Louw have started together since the Premiership final victory last June.
Fly-half Allan and winger Lynagh both return to the starting XV, having come off the bench during the victory over Worcester.
Marshall is a graduate of Newcastle's academy, as is Farrar, who made his debut last season and has only started one Premiership match this campaign so far.
Lucock starts at inside centre with Matias Orlando missing after sustaining a head injury during the defeat by Bath.
Harlequins: Green, Lynagh, Jones, Esterhuizen, Murley, Allan, Care; Marler, Riley, Louw, Symons, Tizard, Lewies (c), Lawday, White.
Replacements: Walker, Kerrod, Collier, Hammond, Jurevicius, Gjaltema, Edwards, Northmore.
Newcastle: Brown, Penny (c), Wacokecoke, Lucock, Radwan, Haydon-Wood, Nordli-Kelemeti; Davison, McGuigan, Tampin, Peterson, Farrar, Robinson, Basham, Marshall.
Replacements: Maddison, Brocklebank, Palframan, Montgomery, Lockwood, Schreuder, Connon, Wright.
Referee: Karl Dickson (RFU).