The first round tie has £16,972 up for grabs for the winner, with the loser getting £5,657.
And with no crowds and a reduced prize fund, a valuable element of the competition for Dave Challinor’s side is the chance to test themselves against Football League opposition.
Since 2010, Pools have faced higher level opposition 12 from a higher level in the FA Cup, including three-matches coming in last season’s third-round cup run.
And ahead of the trip to Salford, we look at how Pools have fared when drawn against such opposition. Scroll down and click through the pages for a recap...
1. 2019/20: Oxford United 4-1 Pools
In January 2020, Hartlepool's FA Cup campaign came to an end at the third round stage following a 4-1 defeat against League One side Oxford United. Mark Kitching gave Pools and early lead which they kept until half-time. But a second half response from the hosts saw them run out as convincing winners following goals from Robert Hall, Shandon Baptiste, Tariqe Fosu and Matt Taylor. Frustratingly for Pools, Oxford went on to play Newcastle United at St. James' Park in the next round. Photo: Jordan Mansfield
2. 2019-20: Pools 1-0 Exeter City (AET)
Pools progressed to the third round of the competition last season following a 1-0 extra-time win over League Two Exeter City. Josh Hawkes netted the winner at Victoria Park to send them through. It's one of only two FA Cup wins for Pools against higher-level opposition in the past decade. Photo: FRANK REID
3. 2019-20: Exeter City 2-2 Pools
A memorable comeback that forced a replay. Pools were down and seemingly out at half-time at St. James's Park last season as they trailed 2-0 before Nicky Featherstone's goal of the season strike and an equaliser from Nicke Kabamba forced Exeter to make a midweek trip to the North East. The match is perhaps best remembered for Ben Killip's amazing triple save in the build-up to Featherstone's goal. Photo: Mark Fletcher
4. 2018-19: Pools 3-4 Gillingham (AET)
Pools were on the receiving end of a two goal comeback when they hosted League One Gillingham for an FA Cup replay back in 2018. Carl Magnay and Paddy McLaughlin put the hosts in control before Max Ehmer and a late Tom Eaves penalty denied Matthew Bates' side a spot in the second round. Luke O'Neill and Elliott List added to the score in extra-time to send Gillingham through with Tyrone O'Neill grabbing a late consolation for Pools. Photo: HUFC