The former Whites man believes his old side should be braced to face more fight from the struggling Millers.
In contrast, Leeds are currently just one point and one place outside the play-off places thanks to a run of form which has seen them win nine and lose just three of their last 13 games in all competitions.
Despite Leeds' home loss to Championship leaders Newcastle United last time out, all the signs would seem to point towards a win for Garry Monk's side.
However, Prutton has stressed that Rotherham will be particularly fired up for the clash with their local rivals, and warned Leeds to expect more fight than has been typically on show from the home side.
Prutton wrote for Sky Sports: "This is a bit of a derby, and for that reason and that reason alone, I think we'll see a bit more fight from Rotherham. But it's not just fight they need, it's quality as well.
"With Leeds having seen the benchmark that Newcastle set, and having worked on the training ground, I think you'll see a Leeds side that want to get back into that top six.
"For a club of that statute, top six is what they should be aiming for this season."
Leeds will be desperate to recover from their home defeat to Newcastle in the best possible fashion by securing a third Yorkshire derby win of the season, having already beaten Sheffield Wednesday and Barnsley.