The two clubs have already met twice this season at Kingston Park, sharing a 17-all draw in the Premiership on 25 September and Quins winning 19-8 in the LV= Cup on 15 November.
Harlequins last six fixtures in the Guinness Premiership have all been won by the home side on the day. The Londoners are unbeaten in their last five encounters at the Twickenham Stoop in the Guinness Premiership.
Newcastle Falcons host Gloucester on Wednesday evening. The Falcons have lost their last four away games in all competitions since their trip to Albi in the Amlin Challenge Cup on 15 January.
Newcastle have lost on their last seven visits to the Stoop since a 20-18 victory on 30 September 2000.
Referee: David Rose (78th Premiership game)