The 2011 winners come into the game off the back of Monday's 1-0 victory over Aston Villa, which keeps alive their hopes of retaining their Premier League crown.
The Tykes last reached this stage in 2008, where they memorably beat Chelsea 1-0 at Oakwell.
Sergio Aguero will miss the tie due to a knee injury so Carlos Tevez, who scored the winning goal against Villa, could retain his place up front. Vincent Kompany may be fit enough to play following a calf injury.
Flitcroft could name the same Barnsley XI which drew 1-1 at Burnley in midweek.
Manchester City: WWWLDD
Possible starting lineups
Manchester City: Hart; Zabaleta, Kolo Toure, Nastasic, Clichy; Milner, Barry, Javi Garcia, Silva; Yaya Toure; Tevez
Barnsley: Steele, Crainey, Kennedy, Wiseman, Etuhu; O'Brien, Perkins, Tunnicliffe, Cywka; Dagnall, O'Grady
Sports Mole says: 2-0