Osbourne, who arrived on loan from Aston Villa on Thursday, is likely to start in the middle of midfield, with Gary O'Neil providing the width.
That means Julio Arca, who operated out wide in last week's defeat to Plymouth, drops to the bench.
Striker Marcus Bent, on loan from Birmingham, also makes his first start for Boro and he will partner Leroy Lita in attack. Marvin Emnes makes way.
In the absence of Emanuel Pogatetz, Jonathan Grounds slots in at left-back. Chris Riggott and Andrew Taylor have been left out, despite travelling to London with the squad.
CRYSTAL PALACE: Speroni; Butterfield, Fonte, Davis, Hill; Ambrose, Derry, Ertl, Danns; Sears, Lee. Subs: Clyne, John, Carle, Moses, Scannell, Djilali, N'Diaye. MIDDLESBROUGH (4-4-2): Jones; Hoyte, Wheater, St Ledger; Grounds, O'Neil, Osbourne, Williams, Johnson; Lita, Bent. Subs: Coyne (gk), McMahon, Franks, Bennett, Arca, Emnes, Yeates.