The Portuguese champions and last season's Europa League winners - also coming in from the Champions League - have lost just once in their domestic competition this season.
Mancini said: "I think this is one of the big games at this stage because we play Porto, a top team who have played Champions League.
"I have met Porto many times in the Europa League or Champions League and it is very difficult to play here.
"At home they are very strong, last year they won the title. It will be very hard for this reason but I think it will be a very good game."