The Blues overcame stiff competition in the last 16 from Serie A side Napoli following a 5-4 aggregate win at Stamford Bridge.
Three-time Premier League champions Chelsea will travel to Estadio da Luz for the first-leg of the encounter, seemingly giving Di Matteo’s side the upper hand over the two matches.
However, the former Blues midfielder, who has steadied the ship after taking over from Andre Villas-Boas earlier this month, says Benfica will be looking to give his side a stern examination when they meet at the end of March.
"When you get down to the last eight teams, any draw is difficult," the former West Bromwich Albion manager said of O Glorioso.
"I've seen Benfica many times. They were in Man United's group. It's a tough game for us.
"I think the fact that we play the first game away for us is good."
Awaiting either Benfica or Chelsea in the semi-finals will be AC Milan or Barcelona, with many expecting an Anglo-Spanish clash in the final four.
However, the 41-year-old has criticised those already writing off the current Serie A league leaders, insisting he has been around long enough to know not to expect anything in football.
"Are you writing off AC Milan straight away, as easy as that - the leaders of Serie A?" he added.
"[We will take it] game by game. That's what I've learnt in my playing career and my coaching career."
'Will Cristiano Ronaldo and Neymar extend their contracts in Saudi Arabia? We play a facilitating job, but it’s down to the players and the clubs to decide' Saudi Pro League chief reveals how talks will work for out-of-contract duo
Nations League: Who are the ITV commentators and pundits for England vs Republic of Ireland?
