The 30-year-old's teammate Phil Foden picked up a second consecutive Young Player of the Season Award earlier on Saturday, and the City duo will be hoping to add this season's Premier League title to their trophy haul when they face Aston Villa on the final day on Sunday.
De Bruyne, who previously won the award in 2020, has made 27 league appearances this season, scoring 15 goals and making seven assists.
Salah was in contention to win the award after netting 22 goals as Liverpool have pushed the Premier League title chase to the wire. The Egypt forward also leads the league in assists (13.)
"To win this award for a second time is an achievement that I am really proud of," De Bruyne said in a statement.
"There is so much quality in the Premier League and it is a pleasure to be nominated with so many other great players who have had incredible seasons for their clubs.
"I think my performances this season have been good and I am happy that I have been able to contribute with goals and assists throughout the season."
City are chasing a fourth Premier League title in five years on Sunday, while Liverpool, who face Wolverhampton Wanderers at Anfield, are bidding to win their third trophy of the season as they chase a historic Quadruple.