"If we are at our level we will go through", Barcelona director Guillermo Amor said.
Cillessen sustained a torn calf muscle during training and will be out of action for their busy February schedule, which sees Barca play seven games.
"We are delighted with him for how he manages the squad and that is important because there are times when it is not easy to live with so many players of that level and that everyone is happy". We expect two intense and even games.
"We trust our players but obviously this is one of the greatest games in the world today".
'Significant snowfall' forecast to bring further disruption and school closures
Up to 10cm of snow is predicted over the next 24 hours, with higher ground more susceptible to receiving a covering. A warning for rain and hill snow giving way to ice in Northern Ireland will last until 10.30am on Tuesday.
The LaLiga giants now occupy third position in the league standings, 10 points behind table-toppers Barcelona.
The El Clasico will hold over two legs as Los Blanocs will be looking to unseat La Blaugrana as champions over the last four years. Betis meanwhile beat Espanyol 4-2 on aggregate, with Valencia overcoming Getafe 3-2 on aggregate by scoring twice in stoppage time in their 3-1 victory in the second leg at Mestalla.
Having put up a good fight in last week's first leg, Girona had high hopes of a comeback and started brightly, with Alex Granell hitting the bar as they pushed for a way back into the tie in the opening exchanges.
"Real Madrid is the best team of the last century and therefore the best team in history".
Barcelona will be looking to reach the final, to be played at Betis' Benito Villamarin in Seville on May 25, and win the competition for the fifth time in a row.