Ronaldo will miss Portugal's Nations League opener against Italy in Lisbon on Monday after the five-time Ballon d'Or winner opted to skip this month's internationals.
The 33-year-old forward – who is yet to open his account for Serie A champions Juventus since arriving from Real Madrid – is Portugal's most-capped player and all-time leading scorer with 85 goals in 154 appearances.
While Portugal felt Ronaldo's absence in a 1-1 friendly draw against Croatia, Mancini is not taking the Euro 2016 winners for granted.
"Portugal won the last European Cup. They are stronger when Ronaldo is playing," Mancini said. "But even without Ronaldo the team is very good with lot of technical players.
"When Ronaldo will not play football anymore, I hope as far as possible for him, Portugal will try to do something different and this is a good chance for them.
"But they are still a great team, even without Ronaldo."
Italy's Nations League campaign opened with a difficult 1-1 draw at home to Poland in Group Three on Friday.