Objective <p>This study aimed to explore the chain mediating effects of interpersonal sensitivity and loneliness in the relationship between neuroticism and depression among Chinese treatment-seeking adolescents recruited from outpatient mental health services. The study sought to understand how neuroticism influences depression through these two mediators.</p> Method <p>A sample of 511 treatment-seeking adolescents was investigated using the Eysenck Personality Questionnaire (EPQ), the Interpersonal Sensitivity Subscale of the Symptom Checklist‑90 (SCL-90), the Illinois Loneliness Questionnaire, and Zung’s Self-Rating Depression Scale (SDS).</p> Results <p>The results showed significant positive correlations among neuroticism, interpersonal sensitivity, loneliness, and depression. Neuroticism predicted depression both directly and indirectly through interpersonal sensitivity and loneliness, which together formed a significant chain‑mediated pathway between neuroticism and depression.</p> Conclusions <p>The findings contribute to a deeper understanding of how neuroticism affects depression in treatment-seeking adolescent populations and provide practical guidance for improving clinical assessment and intervention for adolescent depression.</p>