A Russia 2018 berth is up for grabs as European champions and second-placed Portugal welcome unbeaten Group B leaders Switzerland to Lisbon.
Vladimir Petkovic's side have won all nine of their qualifiers after opening the campaign with a 2-0 victory against Portugal in September last year, when Ronaldo was injured.
But with Ronaldo, who on Tuesday (AEDT) was again nominated for the Ballon d'Or award he won in 2016, back fit and firing having scored against Andorra last week, Pepe is confident Portugal are ready to pip the visitors to an automatic qualifying spot, which they will secure with a win.
"It was our first game and we did not have our most important player, our standard-bearer Cristiano Ronaldo," said Ronaldo's former Real Madrid team-mate Pepe. "It will be completely different.
"I know that what Cristiano wants is to be at the World Cup next year.
"So you can ask him, but I as his friend and knowing his goals, I can guarantee that what Cristiano wants is to help Portugal and win. Win to play in the World Cup.
Ronaldo has scored 15 goals in Portugal's qualifying campaign and could break the European qualifying record held by Robert Lewandowski with a two-goal performance against the Swiss.
"Is there a team in the world that would not be stronger with Cristiano Ronaldo? I don't think so. With Cristiano, it's obvious our team is even more valuable."
"Which player does not want to win? A player who doesn't want to win, it's better not to be with us. Everyone wants to win, players and the Portuguese people," Pepe said.
"It will be a difficult game, but if we are together, players and fans will be difficult for the opponent.
"But we have to do our job and what the coach asks for the team. Let's face the game with competitive concentration."