Problematic smartphone use (PSU) is frequently considered a public health issue, especially in East Asia and Europe. Yet, there is a paucity of research focusing on cultural and familial determinants of PSU. This cross-cultural study aimed to investigate smartphone usage patterns and possible mediating effects of perceived family support (PFS) from a stress-coping perspective. Convenience samples of 790 Chinese and 439 Belgian undergraduates completed an online survey that focused on sociodemographics and psychological variables (i.e., anxiety, depression, PFS, and PSU). In both samples, PSU was positively associated with anxiety and depression, and negatively associated with PFS. However, after controlling for sex and age in structural equation models, the consistent mediating effects of PFS were only found between anxiety and PSU in both cultural settings. These findings suggest that psychological interventions that take into account familial factors could be helpful for young people presenting with anxiety and PSU.