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Rooney, who scored in the third round replay win over West Ham, returns to the starting team, with Danny Welbeck and Robin van Persie starting on the bench.
Also returning to the starting lineup is Nani, with Ryan Giggs, Anderson and Michael Carrick playing from the start as well.
Manchester United manager Sir Alex Ferguson has again decided to stick with David de Gea in goal, while Chris Smalling and Phil Jones start at center-back.
Former Manchester United forward Dimitar Berbatov returns to Old Trafford to face his old club and he reveals that he has nothing to prove.
Manchester United: De Gea; Rafael, Jones, Smalling, Evra; Nani, Carrick, Anderson, Giggs; Rooney, Hernandez.
Subs: Lindegaard, Ferdinand, Kagawa, Scholes, Valencia, van Persie, Welbeck
Fulham: Schwarzer; Riether, Hughes, Hangeland, Riise; Duff, Sidwell, Baird, Kacaniklic; Ruiz, Berbatov
Subs: Etheridge, Senderos, Petric, Karagounis, Briggs, Rodallega, Dejagah
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