Guardiola feels a win will end Real's title hopes.
"Make no mistakes, we are not taking the game for granted," he said.
"We are not going to think as if nothing will happen if we lose at the Bernabeu. This is a unique opportunity for us to strike a decisive blow in the title race. If we lose, the gap will be down to five points with six games left. We must play against Madrid like we did in the last two years.
"They are a team that knows how to hit back, they have a big squad, and they have multiple ways of approaching a game. We have to make a big effort and the players must go for the win. We cannot afford to throw away this game or any other game. That is just not Barca's way."