The Belgium international, out of action since November 1 with a hamstring injury, is one of 10 players to come into the side on the back of the 2-2 draw against Liverpool.
Boss Mauricio Pochettino hinted that he would make mass changes and Son Heung-min is the only player to retain his place in the starting lineup, which is spearheaded by Fernando Llorente at Wembley Stadium.
Tottenham Hotspur: Vorm; Aurier, Alderweireld, Foyth, Rose; Wanyama, Winks; Sissoko, Lamela, Son; Llorente
Subs: Gazzaniga, Trippier, Sanchez, Walker-Peters, Eriksen, Dele, Kane
Newport County: Day, Pipe, White, Demetriou, Butler, Tozer, Bennett, Labadie, Willmott, Nouble, Amond
Subs: Bittner, Dolan, McCoulsky, Reid, O'Brien, Sheehan, Hayes
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