Heckingbottom quit his role at Barnsley to take over from Thomas Christiansen at Elland Road and the 40-year-old faces a big task to get the club back in the Championship play-off picture.
Leeds are currently seven points behind the top six with 16 games to play, but Prutton has tipped them to to pick up a draw at Bramhall Lane on Saturday.
“This is a massive test for Paul Heckingbottom,” Prutton told Sky Sports.
“It’s quite the move he’s made from Barnsley to Leeds for more than one reason and he’ll be under the microscope right away at Bramall Lane.
“When these two sides met in October they were both right in the mix for automatic promotion, and Sheffield United even went top after they won at Elland Road.
“But both have drifted away from the play-offs now and will be desperate for a win. It will be a good, open game, and I think it will be a draw.”
Prutton thinks Leon Clarke will open the scoring for the home side, but he has backed Leeds to fight back and secure a 2-2 draw (60/1 with Sky Bet).
Leeds are without a win in their last seven games in all competitions, while the Blades have won just three of their last eight outings.
Sheffield United are priced at 4/5 to win the game, with Leeds on offer at 18/5. The draw can be backed at 5/2.