The most watched game in world football is Barca's first since Cruyff passed away at the age of 68 after a short battle with cancer last week.
A pre-match display involving over 90,000 fans will read "thank you Johan" with the same message carried on the Barca players' shirts.
"In what is a special match, it is without doubt extra motivation for us to try and win the game," said Barca captain Andres Iniesta.
A 4-0 thrashing of Real when the sides last met in November put Barca well on course to retain the title.
However, with Madrid now under new management since Zinedine Zidane replaced Rafael Benitez in January and with the front three of Cristiano Ronaldo, Gareth Bale and Karim Benzema fit and in scoring form, Iniesta expects a much tougher task on Saturday.
"These games are different, it doesn't matter how the teams are playing before because we all like to beat your biggest rivals," added the Spanish international.
Bale in particular will be well-rested as he was given time off by Wales boss Chris Coleman during the two-week international break preceding the game.
And he is confident that Madrid could drag themselves back into the title race if they can snap Barca's 39-game unbeaten run stretching back to October.
"They are playing very well at the moment so we have to take the game to them," said Bale.
"I believe anything is possible in football. We know we are 10 points behind but we will keep fighting until the league is impossible.
Both coaches should be able to name their strongest
starting line-ups with Barca only missing Jeremy Mathieu and Sandro Ramirez, while Madrid have a clean bill of health.
However, tiredness could play an important factor with two of Barca's deadly front three, Lionel Messi and Luis Suarez, only having arrived back in the Catalan capital on Thursday after playing World Cup qualifiers for Argentina and Uruguay respectively in the past week.
"It would be nice to score my 500th goal against Real Madrid in the Clasico, but it would be even nicer to win the game," said Messi.
Atletico Madrid can close to within six points of Barcelona at the top before kick-off at the Camp Nou as they host Real Betis earlier on Saturday.
However, Atletico coach Diego Simeone could keep a number of players in reserve as they travel to face Barca in the first leg of their Champions League quarter-final on Tuesday.
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