The current study aimed to explore the underlying mechanisms of how interpersonal relationships relieve adolescents’ problematic mobile phone use (PMPU) and to examine the potential mediating roles of loneliness and motivation to use mobile phones. Four thousand five hundred and nine middle school students from four provinces in China were recruited to participate in the investigation. The results showed that the parent–child relationship but not the teacher–student relationship, had a direct and negative effect on PMPU. The parent–child relationship had indirect effects on PMPU through the mediators of loneliness, escape motivation and relationship motivation; the teacher–student relationship had indirect effects on PMPU only through the mediating factors of loneliness and escape motivation. Both parent–child and teacher–student relationships indirectly affected PMPU through a two-step path from loneliness to escape motivation. These findings highlight the more salient role of the parent–child relationship than that of the teacher–student relationship in directly alleviating PMPU and indicate that satisfying interpersonal relationships can buffer adolescents’ PMPU by lowering their loneliness and motivation to use mobile phones.