The coach took the helm of the Italian champions hours before their 1-1 draw with Barca in last month's last-16 first leg and Napoli are now on a six-game unbeaten run in all competitions.
Calzona, like Barcelona boss Xavi Hernandez did earlier in the day, said Tuesday's match is the biggest of the season as a win would confirm his side's improvement since his appointment.
"With Barcelona, the challenge is very important, it's the match of the year, passing the round would mean a lot at a corporate level and enthusiasm for the team," the Italian told a press conference.
"Compared to the first leg, we have changed a lot, now the team is more compact, we concede less, we are able to create more, we are scoring enough, we are defending up front.
"The credit goes to the lads who in three weeks have made giant steps forward. But the path is not finished, we still have a lot to do to become what I would like."
Napoli have dropped out of Serie A title contention as they are languishing in seventh place in the standings, 31 points adrift of leaders Inter Milan, while Barcelona are third in LaLiga.
"If you are afraid you don't even have to show up," Calzona said on facing the Spanish champions.
"You have to have the boldness to face a strong and healthy opponent, but knowing that Napoli can play on equal terms with anyone trying to win games."
Following Friday's 1-1 Serie A draw with Torino, Calzona added that his players must improve as a unit if they are to beat Barcelona.
"Our weapon is to be a team for ninety or one hundred and twenty minutes. The goal of individuals must be achieved through the common goal," he said.
