Background <p>Research on the relationship between these two phenomena has become a focal point in academia; however, the mechanisms through which loneliness affects depression in college students remain unclear. Our findings enhance our understanding of the complex interplay among loneliness, problematic internet use (PIU), and perceived social support in the mechanisms underlying depression in college students, and underscore the importance of addressing depression within interventions aimed at reducing loneliness.</p> Methods <p>The present study, using a sample of Chinese college students, investigates the impact of loneliness on depression and the roles of PIU and perceived social support in this relationship. To explore the relationships among the variables, we employed SPSS and the SPSS PROCESS macro to conduct reliability assessments, correlation analyses, mediation tests, and moderation analyses.</p> Results <p>The results indicate that loneliness serves as a significant positive predictor of depression among college students, with PIU acting as a mediator in the relationship between the two variables. Perceived social support moderates the direct effect of PIU on depression.</p> Conclusion <p>The results suggest that, in light of the direct impact of loneliness on depression among college students, along with the mediating roles of PIU and perceived social support in this relationship, interventions designed to alleviate loneliness are essential for preventing the onset of depression, alleviating depressive symptoms, and mitigating PIU. Educators can collaborate with parents, establish mentorship programs, and enhance the campus environment to provide support. Furthermore, policymakers in higher education and online platform designers can leverage these findings to establish a more supportive environment for mitigating depression risk.</p>