The two footballing giants lock horns at the Santiago Bernabeu in a Group D match and Ajax supervisory board member has backed his side to produce a positive result.
"Normally, Ajax face a difficult evening in Madrid. However, there are plenty of question marks about Real Madrid's form," Cruyff said in his column in De Telegraaf.
"They have been very inconsistent in the opening weeks of the season and you can see that bothers them.
"Ajax have to be very organised. I can see them getting a few chances. Madrid's centre-backs are superb in the duels, but their positioning is rather suspect. I'd say that is their Achilles heel and Ajax could take advantage of that."
Ajax started the group stage with a scoreless draw against Olympique Lyonnais, while Real Madrid beat Dinamo Zagreb 1-0 in their opener.