Manchester United have won the FA Cup 11 times, while Liverpool have triumphed on seven occasions.
There are two other definite all-Premier League ties with West Brom hosting Norwich and Everton welcoming Fulham to Goodison Park.
There are two other potential top flight ties as Arsenal will be at home to Aston Villa if they can overcome Leeds at the Emirates Stadium on Monday night, while Bolton will take on Swansea at the Reebok Stadium if they see off Macclesfield in a replay having drawn 2-2 at Moss Rose on Saturday.
QPR will host west London neighbours Chelsea if they can overcome the MK Dons in a replay at Loftus Road.
Full 4th Round drawBrighton or Wrexham v Newcastle
Sunderland v Middlesbrough
Dagenham or Millwall v Southampton
Hull v Crawley
MK Dons or QPR v Chelsea
West Brom v Norwich
Blackpool v Sheffield Wednesday
Arsenal or Leeds v Aston Villa
Stevenage v Notts County
Watford v Tottenham
Liverpool v Manchester United
Derby v Stoke
Everton v Fulham
Macclesfield or Bolton v Swansea
Sheffield United v Birmingham or Wolves
Nottingham Forest or Leicester v Swindon