<p>In the current era of digitalization, the Internet has become deeply integrated into adolescents’ daily lives. However, issues such as mobile phone addiction have emerged, severely impacting their mental health. Grounded in the cognitive-behavioral model of mobile phone addiction, this study investigates the longitudinal effects of interpersonal stress on mobile phone addiction among adolescents and its underlying mechanisms. A cluster sampling method was employed to recruit 931 participants from three middle schools in a Chinese province for a 6-month longitudinal study. Data were collected using the Adolescent Interpersonal Stress Scale, Mobile Phone Addiction Scale, and Loneliness Scale. The findings revealed that: (1) Adolescents’ interpersonal stress significantly and positively predicted their mobile phone addiction levels. (2) Loneliness exhibited a longitudinal mediating role in the relationship between interpersonal stress and mobile phone addiction. (3) Gender moderates the second stage of the longitudinal mediation. This study elucidates the intrinsic mechanism through which interpersonal stress longitudinally influences mobile phone addiction in adolescents. The results provide theoretical insights for interventions targeting adolescent mobile phone addiction and offer empirical support and practical implications for safeguarding adolescent mental health.</p>