The 21-year-old has enjoyed a stellar start to the season for Los Blancos and is rewarded with his fourth international cap at the home of his club side.
Sergio Ramos once again starts alongside Barcelona rival Gerard Pique at the heart of the defence, while 35-year-old record goalscorer David Villa - back in the squad for the first time in more than three years - only makes the bench.
Italy, meanwhile, welcome Marco Verratti back into the fold as one of two changes for the top-of-the-group clash.
Gianluigi Buffon makes his 170th appearance in goal for the Azzurri, who are currently level on points with Spain at the top of the group but sit in second place due to their inferior goal difference.
Spain: De Gea; Carvajal, Ramos, Pique, Alba; Iniesta, Busquets, Koke; Isco, Asensio, Silva
Italy: Buffon; Darmian, Barzagli, Bonucci, Spinazzola; Candreva, De Rossi, Verratti, Insigne; Belotti, Immobile
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