The Blaugrana will play at San Siro in the first of two last-16 clashes, and Tito Vilanova’s men are the clear favourites despite the Rossoneri’s exceptional form in the last two months.
Berlusconi told La Gazzetta dello Sport: "They are the second team in recent history to [dominate] football; after Milan under [Arrigo] Sacchi, it's Barcelona who have captivated everyone.
“This will be a meeting between a team at the height of success against one which is now starting to develop with a project made up of young people.
“I hope Milan do not look out of place, but certainly it will be very difficult to go and carry out the mission I have always given to Milan.
"This time, Barca will be in control on the field of play, and we will have to fight so as not to be dominated in the game."
When asked if head coach Massimiliano Allegri’s job depends on Milan finishing third, the San Siro chief dismissed the notion and said Milan want to build on what they have right now.
"Third place in the championship is the ambition we have, the goal we have set ourselves. Allegri's future is in his hands, as are the results," he added.
"There were a series of negative results earlier this season and one usually blames the coach.
“However, we have held back, we talked for a long time and we found a union of views on the future of the team.
“In a nutshell, we will not go to buy players that cost a lot, but give us a period of two to three years for a team of young people who can begin a cycle.
“Allegri has agreed on this and [Mario] Balotelli’s signing falls into this decision. Now we are looking for upcoming talent to continue to build."
Milan sit third in Serie A after 25 games, behind table-topping Juventus and second-placed Napoli but above the likes of Inter, Lazio, Fiorentina and Roma.