The Scudetto holders meet last season's Liga and Champions League winners at Camp Nou in what promises to be a mouthwatering encounter.
Milan struggled to a 2-2 home draw with Lazio on Friday in their opening game of the Italian season but the Brazil centre-back remains confident ahead of the match against the Catalan club.
"We are working hard, it will be a difficult game but we'll see," the 27-year-old told Rai Sport.
"We are not facing certain defeat. Every week we know we will face a great team and we must pay attention to the specific characteristics of our opponents.
"For me it's [the Barcelona against Milan game] like playing a derby between the two best sides in Europe. Both will be strong but we will try to win."
Silva joined Milan from Fluminense in December 2008 for €10 million and has since established himself as a fundamental part of the team.
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