The strikers have played together previously but this is their first start as an attacking duo, with Sørloth having replaced Ayew during Sunday's draw with Arsenal.
They will be supported from midfield by Max Meyer, who will also start tonight alongside Jason Puncheon.
In terms of available substitutes, Hodgson's Palace have further attacking options in Connor Wickham and Sullay Kaikai who will share the bench with 18-year-old Nya Kirby.
Palce fans will be pleased to know that Pape Souare is starting, having only appeared in the previous round of the Cup in the 79th minute.
Tony Pulis has made four changes to the previous side he fielded in the Cup and nine from his last league fixture.
Palace: Guaita, Souare, Riedewald, Kelly, Wan-Bissaka, Schlupp, Puncheon, Meyer, Townsend, Sørloth, Ayew. Subs: Speroni, Woods, Milivojevic, Kirby, Williams, Kaikai, Wickham.
Middlesbrough: Konstantopoulos, McNair, Ayala, Batth, Friend, McQueen, Leadbitter, Wing, Tavernier, Braithwaite, Hugill. Subs: Lonergan, Wood, Stubbs, Saville, Chapman, Fletcher, Gestede.
You can find out how the Eagles get on by listening to full commentary on Palace Audio for just £1.49.