The forward has struggled to reproduce his Valencia form since moving to Camp Nou in 2016, and has become a perennial substitute for the Catalans.
But he will start at Camp Nou as Ernesto Valverde preferred Alcacer to Gerard Deulofeu, who drops to the bench.
There is welcome news too on the injury front in the shape of Andres Iniesta, who is available again for selection.
The veteran slots into his usual position in midfield alongside Ivan Rakitic and Sergio Busquets, leaving Paulinho as a substitute.
Thomas Vermaelen, meanwhile, makes the matchday squad for only the second time this season after playing in the Copa del Rey clash against Murcia.
Barcelona: Ter Stegen; Semedo, Pique, Umtiti, Alba; Rakitic, Busquets, Iniesta; Messi, Suarez, Alcacer.
Substitutes: Cillessen, Denis Suarez, Mascherano, Paulinho, Deulofeu, Digne, Vermaelen.
Sevilla: Soria; Corchia, Kjaer, Lenglet, Escudero; Banega, Pizarro, Nzonzi; Navas, Sarabia, Muriel.