The 31-year-old sustained a calf injury during the warm-up at Wakefield Trinity last week and had to watch KR’s 56-12 victory from the sidelines.
After undergoing a scan on Tuesday, Hadley has been ruled out of the Craven Park eliminator against the Leopards in a blow for Rovers.
Hadley has played 25 games in a variety of positions in Willie Peters’ pack this season.
The hardworking Hull native has been replaced in the 21-man squad by Jimmy Keinhorst, who has recovered from an ankle injury.
In the only other change, prop Rhys Kennedy returns in place of half-back Rowan Milnes after overcoming the illness that ruled him out of the final game of the regular season.
Kane Linnett was a late withdrawal ahead of the Wakefield match with a calf injury but the veteran second-rower is all set to return against Leigh.
Hadley and Sam Wood are the only players unavailable to Peters for the first round of the play-offs.
Zak Hardaker misses out for the Leopards with a broken thumb but Adrian Lam has included John Asiata in his 21-man squad alongside Tom Amone, who saw a one-match ban overturned on appeal.
Asiata has not played since September 3 because of a hamstring problem.
Former Rovers back-rower Frankie Halton returns to face his old club and Oliver Gildart is set to meet his future employers but Leigh remain without powerful centre Ricky Leutele.
Hull KR 21-man squad: Ethan Ryan, Tom Opacic, Shaun Kenny-Dowall, Ryan Hall, Jordan Abdull, Jesse Sue, Matt Parcell, George King, Kane Linnett, Elliot Minchella, Jez Litten, Rhys Kennedy, James Batchelor, Matty Storton, Jimmy Keinhorst, Mikey Lewis, Louis Senior, Sam Luckley, Yusuf Aydin, Jack Walker, Brad Schneider.
Leigh Leopards 21-man squad: Tom Briscoe, Ed Chamberlain, Josh Charnley, Joe Mellor, Lachlan Lam, Tom Amone, Edwin Ipape, Robbie Mulhern, Joe Wardle, Jack Hughes, John Asiata, Ben Nakubuwai, Ben Reynolds, Oliver Holmes, Gareth O'Brien, Matt Davis, Tom Nisbet, Kai O'Donnell, Ava Seumanufagai, Frankie Halton, Oliver Gildart.