The local rivals are expected to draw a good crowd at Victoria Park for an encounter that has caught the imagination in the north-east.
Blyth, who inflicted one of the most famous cup upsets at the expense of Stoke City en route to the fifth round in the 1977–78 campaign, will take heart from the lowly position of opponents sitting bottom of the Football League.
However, manager Tom Wade knows the Northern Premier League Premier Division side will have to produce a special performance in order to reach the third round.
“The spirit in the camp is really good,” Wade told the Hartlepool Mail. “We are in a rich vein of form at the moment and have only lost a few times in the last 15 matches.
“We are confident of performing well and playing as well as we can but we have to go there and play out of our skins, while they need to have an off-day. But anything could happen.”
Hartlepool boss Paul Murray has also talked up the importance of the fixture, with his side having secured only three wins in League Two this season and facing a battle to stay in the Football League.
“It is a huge game and I am very much looking forward to it and the players are positive and bright,” said Murray. “We know what they will be all about and what they want to do to us.
“We will work this week on what we are going to do. It’s a difficult time anyway for the club and Friday is a big game for all. But we are strong enough to go and get a result.”
Blyth are not the only non-League side hoping to cause an upset, with Dartford travelling to Bradford City on Sunday, while Telford United will attempt to spring a major surprise at League One leaders Bristol City.
Also on Sunday, Dover Athletic travel Cheltenham Town, Worcester City make the trip to Scunthorpe United, Chester head to Barnsley and Aldershot Town welcome Rochdale.
There will be at least three non-League outfits in the third-round draw, given Wrexham meet Maidstone United on Saturday, Gateshead tackle Warrington Town and Southport host Eastleigh on Sunday.
The remaining 10 fixtures are all-Football League affairs.
Oldham Athletic face League One rivals Doncaster Rovers at Boundary Park on Saturday, Chesterfield travel to MK Dons and Colchester United clash with Peterborough United in the final tie of the weekend on Sunday.
Four are all League Two matches, with Bury taking on Luton Town, Cambridge United tackling Mansfield Town, Oxford United going up against struggling Tranmere Rovers and Wycombe Wanderers meeting AFC Wimbledon.
It will be League One versus League Two in the final trio of matches as Sheffield United battle Plymouth Argyle, Accrington Stanley welcome Yeovil Town and Shrewsbury Town travel to Preston North End.
