Harlequins last eight games in the Guinness Premiership have all been won by the home side on the day, whilst Quins most recent away victory in the competition was 30-27 at Leeds on 4 December.
Saracens return to Wembley Stadium for the fourth time this season, having achieved three narrow wins there so far: 19-16 over Northampton in the Guinness Premiership, 24-23 over South Africa and 25-20 over Worcester also in the Premiership.
Saracens won 22-9 at the Stoop when the two clubs met in round three.
Referee: Martin Fox (57th Premiership game)
Live on Sky Sports HD.