BACKGROUND: This study drew on social ecosystem theory, the comprehensive model of family socialization and the multiple-attachment theory to explore three key aspects: the association between family functioning and depressive symptoms in primary school children, the mediating role of friendship quality and the moderating role of teacher-student relationship in these associations. METHODS: A total of 1024 students in Grades 4 through 6 from five schools in Hunan Province were surveyed using the Short Form of the Center for Epidemiological Studies Depression Scale, the Family Caring Index Questionnaire, the Friendship Quality Questionnaire (FQQ) and teacher-student relationship Subscale of the 'My Class' questionnaire. RESULTS: (1) Depressive symptoms were significantly negatively correlated with family functioning, friendship quality, and teacher-student relationship. (2) Family functioning was significantly associated with depressive symptoms in primary school children. (3) Friendship quality mediated the relationship between family functioning and depressive symptoms. (4) Teacher-student relationship moderated the relationship between family functioning and friendship quality, as well as between friendship quality and depressive symptoms in primary school children. CONCLUSIONS: Effective family functioning was significantly associated with improved friendship quality in primary school children, which in turn was associated with lower depressive symptoms. This association was further strengthened by a positive teacher-student relationship. These findings provide valuable insights for developing collaborative interventions within the family-school framework to address childhood depression.