The Championship part-timers host opponents who earned promotion last season via the same competition but now face a relegation battle after finishing second-bottom in Super League.
Duffy, who takes charge of his first game at Post Office Road since replacing sacked Jon Sharp, believes that will aid his own side as they seek to cause a upset.
“I don’t think Leigh have always liked coming to Featherstone,” he said. “We have got an opportunity to perform really well and give a good account of ourselves.
“We’ve set some targets through the next few weeks and – like the other Championship teams – we want to beat the Championship teams. Anything else will be a bonus.”
Featherstone lost their opening game under the former Swinton Lions coach in Toulouse but have now had time to get to grips with his approach.
“It has been a whirlwind couple of weeks for the players with a new coach coming in, but we are trying to take a bit of a fresh approach,” Duffy added.
“We want the players to enjoy it; these are exciting times and they have bought into what we are doing. We are looking forward to seeing how we go. Preparations have been really good.”
Featherstone are set to give a debut to new signing Conor Farrell after the second-row’s arrival from Wigan Warriors.
Fellow part-timers Halifax head to Championship league leaders winners Hull KR in their Qualifiers opener tomorrow hoping to repeat their recent shock.
Richard Marshall’s side stunned Rovers by beating the promotion hopefuls in their last match, the final regular round 28-6 victory at The Shay which dramatically secured them a spot in the Middle Eights.
That was just KR’s third league defeat of the entire season – they also lost at home to Toulouse the week before – but they were without a raft of key players.
Marshall admitted: “We were really pleased with how we performed against a strong Hull KR team last time out.
“We know they will be stronger this time – Shaun Lunt will come back in and Mose Masoe will probably play and whoever else – but we’re confident.
“We’ve got momentum going in and, though it’s never easy playing over in Hull, we did a good job there earlier in the year.
“I think we were only one try adrift going into the last 10 or 15 minutes so we weren’t far off and this doesn’t daunt us.
“It will be a different challenge this weekend as their season relies on beating sides like us in the Qualifiers.
“And they will be confident. They’ve been good in the Championship all year.
“Obviously, in the last two games they have fallen away but I do think they had one eye on the Qualifiers then.
“We’ve gone the other way and built into the Qualifiers with four wins; we’ve actually got better and that makes it a great tie.
“On paper, the teams are poles apart financially but if you work hard from one to 17 anything is possible and we know that.”