The Manager has handed a Palace debut to 18-year-old Italy international Honest Ahanor in defence in tonight's third-round tie.
There are also first competitive starts for fellow new arrivals Óscar Mingueza; Ben Chilwell (in his second spell with the club, having come off the bench to win Saturday's game); and Darío Osorio.
There are also first starts of the season for goalkeeper Walter Benítez, who memorably saved two penalties at this stage against Millwall last season; Will Hughes, who takes the captain’s armband tonight; and forward Jørgen Strand Larsen.
Rested from the squad which won at Fulham are Dean Henderson, Jaydee Canvot, Chris Richards and Eddie Nketiah, with Anan Khalaili, Tyrick Mitchell, Adam Wharton and Daichi Kamada moving to the bench after Craven Cottage.
Middlesbrough manager Kim Hellberg also makes eight changes to his starting XI from the side which won 1-0 at QPR on Saturday, with Sol Brynn, Callum Brittain, Luke Ayling, Alfie Jones, Sam Byram (debuting), Myles Peart-Harris, Amario Cozier-Duberry (debuting), Tommy Conway and David Strelec all starting.
Sebastian Berhalter, son of former Palace player Gregg Berhalter, is on the bench.
Sage's side were one of eight seeded teams who went straight into the third round this season due to our participation in the UEFA Europa League.
Championship outfit Middlesbrough, meanwhile – who won the competition in 2004 – reached the third round after overcoming Wrexham 1-0 at home in the first round, and then League One team Doncaster 3-1 away last week.
If tonight’s tie is level after 90 minutes, it will go straight to penalties to decide who advances; extra-time is only used in the Carabao Cup from the semi-finals onwards.
Palace: Benítez (GK), Tomiyasu, Disasi, Ahanor, Mingueza, Timber, Hughes, Chilwell, Pino, Osorio, Strand Larsen.
Subs: Matthews (GK), Mitchell, Khalaili, Lerma, McNeil, Kamada, Wharton, Gozo, Guessand.
Middlesbrough: Brynn (GK), Brittain, Ayling, Jones, Malanda, Byram, Peart-Harris, Morris, Cozier-Duberry, Conway, Strelec.
Subs: Vitek (GK), Phillips, Borges, Arfsten, Barron, Berhalter, Pukstas, Lankshear.