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With the rapid pace of economic development and intensifying social competition, adolescent depression has emerged as an escalating global public health concern. The present study investigated the relationship between family functioning and adolescent depression, with particular attention being paid to the parallel and serial mediating roles of academic stress and emotion regulation strategies. A total of 437 adolescents from Anhui Province were surveyed using the Chinese versions of the Family Assessment Device, the Academic Stress Scale, the Emotion Regulation Questionnaire, and the Center for Epidemiologic Studies Depression Scale (CES-D). The results revealed that (1) the prevalence of depression was 27.7%, with 31.2% of participants experiencing moderate to high levels of academic stress; (2) family functioning was identified as a key predictor of adolescent depression; and (3) academic stress and expressive suppression sequentially mediated the relationship between family functioning and depression, while academic stress and cognitive reappraisal functioned as parallel mediators. In conclusion, healthy family functioning plays a crucial role in reducing adolescent depression, both directly and through the mediating effects of academic stress and emotion regulation strategies. These findings highlight the importance of family support and the adoption of adaptive coping mechanisms in promoting adolescent mental health.