It is almost 40 years since the Iron last defeated a top flight team in this competition, with victory over Sheffield Wednesday.
Mirfin - was part of the Huddersfield side that defeated Birmingham City in the third round two years ago - is hoping to end that long wait against Roberto Mancini's men.
He told the Scunthorpe Telegraph: "Their manager is new to the FA Cup, so how he sees it, we don't know. But it has always had romance and tradition and I think that is seen abroad as well, not just in England.
"I'm sure Mancini will have been told too by the English staff how important it is, but he knows what his priorities are and he's got players good enough if he chooses to change it.
"They might have one eye on the Carling Cup, but then they've got two international squads they could probably put out. Whoever plays it's going to be tough, but it's a game we're looking forward too."