Background and aim: Problematic mobile phone use (PMPU) is prevalent and increases the risk for a variety of health problems. However, few studies have explored the neural mechanisms that might render adolescents more or less vulnerable. Here, we aimed to identify whether PMPU is associated with depressive symptoms and whether this relationship is moderated by intrinsic functional connectivity (iFC) which is associated with PMPU. Methods: In this longitudinal study, we included 238 students (mean age 5 19.05, SD 5 0.81) that came from a university in Hefei, China. They all finished MRI scans at baseline and completed questionnaires both at baseline and 1 year later. A self-rating questionnaire for adolescent problematic mobile phone use and depression anxiety stress scale-21 were used to assess PMPU and depressive symptoms. We first assessed the relationship between PMPU and depressive symptoms using an autoregressive cross-lagged model. Then, we detected the brain regions that were associated with PMPU. Moreover, the neuroimaging results were extracted to explore whether the iFC of these brain regions moderated the relationship between PMPU and depression. Results: Consistent with our hypotheses, PMPU was positively associated with depressive symptoms, and the relationship between PMPU and depressive symptoms was moderated by iFC of the left parahippocampal gyrusright middle temporal gyrus both at baseline and after 1 year (b 5 0.554, P 5 0.003; b 5 0.463, P 5 0.016, respectively). Conclusions: These results advance the understanding of PMPU and suggest that iFC of the left parahippocampal gyrus-right middle temporal gyrus may be a neurobiological contributor to its relationship with depressive symptoms.  Kulcsszavak: smartphone addiction, depression, moderate effect, resting-state, MRI