Nomophobia is a situational phobia in which a person experiences fear of not being able to use the smartphone. The Nomophobia Questionnaire (NMP-Q) is the most widely used but it is not validated in the Spanish-speaking Latin American context. There are hardly any cross-cultural studies of nomophobia. The main objectives are to:1) adapt and validate the NMP-Q in a Mexican sample; 2) analyse gender, age and cross-cultural invariance; 3) examine the differences between countries. The Mexican sample consisted of 19,226 participants (63.1% girls), and the Spanish sample of 3897 (46% girls), aged between 14 and 19 years. The model of four-factors explained by a second-order factor fitted the data adequately. Satisfactory reliability indices were obtained, invariance by sex and age, and cross-cultural invariance. Higher scores were found in females, in adolescents aged 14–16 years, and in the Spaniards. The NMP-Q allows identifying problems of nomophobia in Mexicans and comparing them with Spaniards.