Last season's beaten finalists currently sit in second place in the Premier League table and have won all but one of their last last 12 matches in all competitions
City were denied their sixth success in the competition by Ben Watson's late strike in the match at Wembley in May but they have only lost one of their last 11 home FA Cup matches.
Manuel Pellegrini's side are the leading scorers in the top four divisions of English football this season with 57 goals in 20 league matches, although the Chilean may opt to rest some of his players for the trip to Ewood Park.
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Manager Gary Bowyer has brought stability to the club following a turbulent campaign last season, and that has been rewarded with only three defeats at home.
City's 3-2 win at Swansea on Wednesday was their fourth away victory of the Premier League season and extended their unbeaten run in all competitions to 12 matches, but Rovers have only lost three of their 12 games at home.
The visitors will provide a real test to that record, with Pellegrini's side unbeaten in their last nine meetings with Blackburn.
Jordan Rhodes will certainly give City's defence something to think about; the Scotland international has scored 16 goals in the league this season and netted in the New Year's Day triumph at Elland Road.
The sides have met six times in the FA Cup, but have only played once in the competition since 1969. Blackburn won that game 2-0 in 2007 thanks to goals from Aaron Mokoena and Matt Derbyshire.
David Silva returns from suspension for City, but Martin Demichelis (hamstring), Sergio Aguero (calf), Stevan Jovetic (illness) and Micah Richards (hamstring) are all still struggling to be fit.
Blackburn have no injury concerns and will have Jason Lowe available after his one-match ban.