Last Friday Keys comprehensively took the League encounter 35-7 but that will mean little when the sides line up for the second time.
Neath give last week's team a huge vote of confidence and make only one change with fit-again Ryan Evans replacing Lloyd Phillips. There is also a welcome return on the replacements bench for Gareth King.
Coach Patrick Horgan said: "This is a very big game for the club. Neath have a great record in the Cup and it's a competition that we really want to do well in the season.
"We know it's going to be tough. Cross Keys showed us last week why they're in the top three. The interception tries put a gloss on the score but it only goes to show how sharp they are and we must be spot on in our accuracy of pass.
"As the selection shows, we have every confidence in the team's ability. We can't argue with the score but strangely the statistics from last week's game were not bad but we must improve on last week's showing. The measure of a side is how it reacts in adversity - this is our chance and the pressure is all on Keys.
"We did not always get the rub of the green or the decisions last week and are overdue a bit of luck and, while Keys see themselves as favourites, we can bounce back."
Keys make three changes to the side that won at the same venue last Friday evening in the Principality Premiership.
Nathan Trowbridge comes in on the wing in place of Luke Williams, Rhys Miller makes his first start at hooker since returning to the club and Anthony Lott is replaced by Craig Gould at tight head prop.
Neath: 15 Aaron Bramwell 14 Bowdy Davies 13 Ryan Evans 12 Dean Cummins 11 Chris Morgans 10 David Langdon 9 Luc Jones, 1 Roy Jones 2 Rhodri Clancy 3 Marc Jones 4 Rhys Jones 5 Jonny Griffiths 6 Lee Evans (c) 7 Leon War 8 Steffan Jones.
Replacements: 16 Rowan Davies, 17 Alun Wyn Davies, 18 Ceri Jones, 19 A.N.Other, 20 Matthew Rees, 21 Gareth King, 22 Lloyd Phillips, 23 Kevin James
Cross Keys: 15 Gareth David 14 Kristian Baller 13 Leon Andrews 12 Luke Ford 11 Nathan Trowbridge 10 Dorian Jones 9 Rhys Dyer, 1 Richard Cornock 2 Rhys Miller 3 Craig Gould 4 Danny Hodge 5 Ollie Hodge 6 Tom Lampard 7 Rob Nash (c) 8 Adam Powell.
Replacements: Anthony Lott, James Johnstone, Sean Higgins, Scott Matthews, Ryan James, Dean Gunter, Luke Williams.