It would depend upon who was addressed, and whether it is more than one person. The singular and plural formal you as compared to the singular and plural familiar would be:
'What (do) you mean?' = '¿Qué quiere / quieren / quieres / queréis decir?'
ANALYSE:
Usted (formal singular, both genders)
Ustedes (formal plural, both genders)
Tú (informal singular, both genders)
Vosotros, as (informal plural, masculine / feminine)
Qué --- What?
Que --- That, which, who (relative clause)