The Toon were held at home to a goalless draw last month and now the two will need a replay to settle the tie.
A trip to Championship leaders West Brom awaits this evening's winner in the fifth round.
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Oxford United vs Newcastle: How to listen
The FA Cup fourth round replay will get under way at 8:05pm on Tuesday, February 4.
Full commentary from the Kassam Stadium will be live on talkSPORT 2, with our coverage starting at 7pm.
Ian Danter and David Connolly will bring you all the build-up and match action.
To tune in, just click here for the live stream or click the radio player below.
Oxford United vs Newcastle: What has been said?
Oxford United manager Karl Robinson: “We know we have a massive job on our hands and we are going to have to play a lot better than we did in the first meeting if we want to get through and have a chance of playing for a place in the quarter-final.
“It’s a massive ask. Our odds will be very long and we are big underdogs, but I don’t mind that. Ultimately, what happens is down to us…”
Newcastle United head coach Steve Bruce: “They [Oxford] are a decent side. It’s live on the TV and they’ll want the underdogs to turn us over, so we have to be wary of that.
“If we can go and get to the fifth round this week and be on 31 league points, I think we’d have accepted that, no matter how we got there. In difficult circumstances over the last month we’ve shown a certain amount of resilience to get us this far.”
Oxford United vs Newcastle: Confirmed line-ups
Oxford: Eastwood, Long, Dickie, Moore, Ruffels, Sykes, Gorrin, Brannagan, Browne, Mackie, Holland.
Subs: Stevens, Hanson, Mousinho, Kelly, Thorne, Agyei, Taylor.
Newcastle: Darlow, Schar, Lascelles, Lejeune, Yedlin, Ritchie, Bentaleb, Matty Longstaff, Sean Longstaff, Almiron, Joelinton.
Subs: Elliot, Clark, Saint-Maximin, Hayden, Fernandez, Atsu, Allan.
League One Oxford United host Newcastle of the Premier League tonight in an FA Cup fourth round replay.