Jose Mourinho's side are currently trailing Barca by eight points after only six games, and Cruyff believes they will find themselves in a precarious situation if they are beaten in the Clasico.
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"If they lose this one it is like having the whole world falling over you. These are normally the games I fear the most. Madrid will do more than everything to change this situation around.
"Mourinho will be under a lot of pressure after Sunday if they lose. Then there is a big problem.
"It could be [a tipping point]. If [they] play seven or eight games and - if he loses - they will be so far behind [Barca]. There’s no excuse [for that]."
Sunday's encounter is scheduled to kick off at 19:50CET.