•The associations between presence of meaning, search for meaning, self-control, and psychological distress were examined in Chinese and Italian adolescents.•Presence of meaning and search for meaning was negatively and positively related to psychological distress.•Self-control mediated the “meaning in life – psychological distress” link.•The direct and indirect effects were similar in magnitude across both samples. Meaning in life refers to the sense made of, and significance felt regarding, the nature of one's being and existence and includes two dimensions (i.e., presence of meaning and search for meaning, Steger et al., 2006). This research aimed to: (1) compare the mean level differences in presence of meaning and search for meaning among Chinese and Italian adolescents; (2) examine the association between presence of and search for meaning and psychological distress; (3) test self-control as a mediator in the aforesaid relationship, and (4) compare the direct and the indirect effects between the two samples. To this end, self-report questionnaires were administered to Chinese (N = 270) and Italian (N = 279) adolescents. Results showed that Chinese adolescents reported greater search for meaning than their Italian counterparts. Moreover, presence of meaning was negatively related to psychological distress whereas search for meaning was positively related to psychological distress, through self-control in both samples with similar magnitude. Collectively, the findings contribute to the knowledge about the influence of meaning in life on adolescent psychological health and the underlying mechanisms. The dialectic model of meaning in life, a model that assumes cultural differences in presence of meaning and search for meaning, is partially supported.