The home side are currently 18th in the table, one point behind 17th-placed Lecce, while SPAL are rock bottom of the division, nine points from safety with seven games left.
Genoa have not played outside of Italy's top flight since the 2006-07 campaign, but they are in serious danger of dropping into Serie B for the 2020-21 season.
The Griffins have only won six of their 31 league matches this term, while they have picked up just 27 points, which has left them in 18th position in the table.
Davide Nicola's side are only a point behind 17th-placed Lecce, though, and will therefore still be confident of escaping the bottom three before the season comes to an end.
Genoa are yet to win since returning to the field last month, though, losing three of their five matches, including a 2-1 home defeat to Napoli on Wednesday night.
Interestingly, each of the last four Serie A matches between Genoa and SPAL has finished 1-1, and the table suggests that there will not be too much between them once again.
SPAL, as mentioned, are bottom of the table, having only picked up 19 points from their 31 matches, and they have a serious task on their hands to escape the relegation zone.
Indeed, the White and Blues are nine points behind 17th-placed Lecce, meaning that they will need to deliver an impressive points return in their final seven games to stay in the league.
Luigi Di Biagio's side picked up a point at home to AC Milan at the start of July but have lost their last two games, both 3-0, to Sampdoria and Udinese.
The fact that two of SPAL's next four matches are against Inter Milan and Roma makes this weekend's contest even more important for a side that are battling for their lives.
One player has particularly impressed for the strugglers this term, though, with 25-year-old forward Andrea Petagna delivering an impressive 12 goals in 29 league appearances.
Genoa Serie A form: WLDLDL
SPAL Serie A form: WLLDLL
Petagna started as the lone forward in a 4-5-1 formation against Udinese and that is again expected to be the case in this match, with Marco D'Alessandro keeping his spot out wide.
Genoa possible starting lineup:
Perin; Masiello, Zapata, Goldaniga; Barreca, Behrami, Schone, Cassata, Biraschi; Sanabria, Pinamonti
SPAL possible starting lineup:
Letica; Sala, Vicari, Bonifazi, Felipe; D'Alessandro, Missiroli, Valdifori, Castro, Murgia; Petagna
We say: Genoa 1-0 SPAL
There is simply no downplaying the importance of this match to both teams, and a defeat for SPAL could be terminal in terms of staying in the league. We are expecting a tight game but fancy Genoa to pick up a huge three points courtesy of a one-goal success.