Atletico humbled Barcelona in last month's first leg, netting four goals in the first half, as Flick's men failed to score in a domestic match for the first time this season.
But Barcelona, who are top of the table in their LaLiga title defence, are not willing to give up on defending their Copa del Rey title, Flick told reporters on Monday.
"We are four goals behind, and we have to make the impossible possible. That is the objective. It’s not easy. However, we will not give up," the coach said.
"It is important to keep a clean sheet, but we must believe in our strength and that we can achieve it... You must always believe. For example, in each half we need to score two goals."
Barcelona, who lead the LaLiga scoring charts with 71 goals this season, have netted seven goals in their last two games, with Lamine Yamal scoring a hat-trick against Villarreal on Saturday.
Barcelona, however, will be without striker Robert Lewandowski, after the Poland international fractured his eye socket during the game against Villarreal.
“We will have to manage Lewy’s absence. We have not had much luck. Losing a player like him, and the others who cannot be there, is a problem, but the team handles it well," Flick said.
"We must press them, win the duels and make things difficult for them. We cannot lose possession, as they are very dangerous in transition... we have to play as one, especially tomorrow."