The Portugal international is under the spotlight following his stamp on Lionel Messi in the first leg, but Guardiola does not want the Camp Nou crowd to vocalise their unhappiness with the defender's action.
"Let us leave Pepe alone," Guardiola told a news conference. "If his coach wants him to play, then let him play and I hope this will be the best possible possible for everyone.
"I hope that what happened with [Luis] Figo will not be repeated because the club's fans regret what happened.
"If it happens again, it means we have not learned anything and that we are not the club we have to be. It would hurt more than to be eliminated."
Pepe, who did not make the squad for Sunday's 4-1 victory against Athletic Bilbao, will know whether he is to face punishment for his action after the Spanish Football Federation (RFEF) convenes on Wednesday.
On Monday, Barca president Sandro Rosell called on RFEF to follow the example of England's Football Association (FA) and punish Pepe after Manchester City's Mario Balotelli was charged with violent conduct following a stamp on Tottenham's Scott Parker.
Questioned about Barca's approach to Wednesday's contest, Guardiola stressed he is only targeting a victory, despite his side's 2-1 advantage in the tie.
"I do not want anyone to think that we have won because the match will be very close and the two teams will have a chance to go through until the last minute.
"If we try to hold out for the result of the [first-leg], they will eliminate us."
The second-leg of the Copa del Rey Clasico kicks off at 22.00CET.
Starting in November and continuing through to the middle of February, Goal.com is publishing exclusive extracts from Graham Hunter's highly-anticipated new book, 'Barca: The Making of the Greatest Team in the World'. Friday's extract looks at how Barca suffered rare disappointment at the hands of Real Madrid in a gripping finale to last season's Copa del Rey. Don't miss it!