The Naples side go into the match at the Stadio Olimpico on the back of Saturday's 3-0 defeat at Atalanta.
Roma, meanwhile, are fully rested after their home match against Parma at the weekend was abandoned after just eight minutes because of a waterlogged pitch.
"I believe Roma are favourites because they have not played at the weekend," Benitez said in Tuesday's press conference. "It's not an excuse, it's the truth."
Benitez has demanded an improved performance from his players at Roma.
The Azzurri endured one of their worst defeats in Serie A this season in Bergamo, a reverse that extended Napoli's winless run to three league games.
"We made a lot of individual mistakes against Atalanta, which is unusual," Benitez said. "However, we didn't play well and I expect a better performance at Roma."
Gonzalo Higuain, Marek Hamsik and Lorenzo Insigne are all expected to start having been benched against Atalanta.
Napoli lost 2-0 at Roma in the league earlier this season but Benitez remains optimistic his side can surprise the Giallorossi in Rome.
"We played well against them back in October," he said. "In that game we had chances to score but we didn't make the most of them.
"My team is calm and charged up for tomorrow's match, knowing that we will also have the return leg (February 12) to look forward to."
Rivals Roma are second in the standings, six points clear of third-place Napoli and have a game in hand.
The Giallorossi, who were runners-up in the Coppa Italia last season, want to take a giant step towards a final spot on Wednesday.
"We want to get the job done tomorrow," Roma coach Rudi Garcia said. "But we are aware that the semi-final is not just one game but 180 minutes and we will also have to play at Napoli.
"It will be great to go to Naples with a good result.
"The fact that we didn't play at the weekend could be an advantage but we will only know that after tomorrow's match."
Garcia is expected to bench striker Alessandro Florenzi and captain Francesco Totti against Napoli in view of Sunday's city derby against Lazio, with Adem Ljajic set to lead Roma's attack.