The United goalkeeper was flattened in midweek by West Ham striker Andy Carroll during his side's 2-2 draw.
And on the eve of Villa's trip to Old Trafford, Guzan has told the young Spaniard that he could be in for another tough 90 minutes.
Guzan said: "Christian is a physical presence - with his height alone he is massive. We know that is one of his many strengths.
"For De Gea, it is about how here responds to the challenges he has to deal with.
"Christian is a handful with his ability in the air. He's so strong and always a force to be reckoned with."
Aston Villa go to the league leaders knowing that even a point could go a long way to securing their Premier League status for another season.