Previous studies showed that loneliness and psychological distress are related. However, the potential mechanisms involved in this relationship are unknown. This study examined the mediating effect of mobile phone addiction and the moderating effect of core self-evaluation on the relationship between mobile phone addiction and psychological distress. A total of 826 college students were recruited. A cross-sectional study design and an online questionnaire survey were employed to measure loneliness, mobile phone addiction, core self-evaluation, and psychological distress in college students, and used the PROCESS macro program to conduct moderated mediation analysis. Loneliness was significantly and positively associated with psychological distress, mobile phone addiction partially mediated the relation between Loneliness and college students' psychological distress and this indirect path was moderated by core self-evaluations. Specifically, the effect of mobile phone addiction on psychological distress was stronger for college students with lower core self-evaluations than for those with higher core self-evaluations. The results are helpful to comprehend the producing mechanism of psychological distress and provide a theoretical basis for the intervention of psychological distress.