Santos revealed during his pre-match press conference that he "didn't like" Ronaldo's reaction to being substituted in Portugal's 2-1 group-stage defeat against South Korea last time out.
The 37-year-old will now begin on the bench at Lusail Stadium and is not starting for Portugal at a major tournament for the first time since 2008 (also against Switzerland).
Ronaldo is one of eight changes made by Santos to his first XI following Portugal's defeat to South Korea, which also sees Manchester City's Joao Cancelo named on the bench.
Raphael Guerreiro and Diogo Dalot have been selected to start as the full-backs at the expense of Cancelo, while Ruben Dias returns at centre-back alongside 39-year-old Pepe.
Bernardo Silva, William Carvalho and Otavio replace Matheus Nunes, Ruben Neves and Vitinha in centre-midfield, while Benfica striker Goncalo Ramos starts ahead of Ronaldo in attack.
Ramos is joined up front with Joao Felix, with Bruno Fernandes set to operate just behind in the number 10 role, while Ricardo Horta and Joao Mario - who started in attack against South Korea - will begin on the bench this evening.
As for Switzerland, Murat Yakin has made two changes to his starting lineup, with goalkeeper Yann Sommer recovering from illness to replace Gregor Kobel between the sticks.
Versatile Mainz 05 midfielder Edimilson Fernandes is handed his first start of the tournament at right-back at the expense of Silvan Widmer, joining Fabian Schar, Manuel Akanji and Ricardo Rodriguez in the back four.
Granit Xhaka, Remo Freuler and Djibril Sow all retain their places in centre-midfield, while Xherdan Shaqiri in joined in attack by Breel Embolo and Ruben Vargas.
Portugal starting lineup: Costa; Dalot, Pepe, Dias, Guerreiro; Otavio, Carvalho, B. Silva; Fernandes; Felix, Ramos
Subs: Patricio, Palhinha, Ronaldo, Andre Silva, Sa, Leao, Mario, Neves, Cancelo, Ricardo, Nunes, Antonio Silva
Switzerland starting lineup: Sommer; Fernandes, Akanji, Schar, Rodriguez; Freuler, Xhaka, Sow; Shaqiri, Embolo, Vargas
Subs: Kobel, Omlin, Kohn, Zakaria, Seferovic, Steffen, Aebischer, Fassnacht, Comert, Frei, Elvidi, Rieder, Jashari