The internet has evolved into an integral facet of the life and educational experience of college students. However, the driving force behind problematic internet use in medical students remains largely unexplored. Based on the cognitive-behavioral model and the affect regulation model of vulnerability, the present study seeks to investigate the underlying mechanism of the association between rejection sensitivity and problematic internet use among medical students. A total of 435 undergraduate medical students were investigated using the Tendency to Expect Rejection Scale, Loneliness Scale, Self-control Scale, and Problematic Internet Test. The results revealed that rejection sensitivity could positively predict loneliness and problematic internet use. Mediation analyses revealed that loneliness served as a mediator in the link between rejection sensitivity and problematic internet use. Additionally, self-control moderated the second stage of the indirect effects in the relationship between rejection sensitivity and problematic internet use. These findings theoretically deepen our understanding of the psychological pathways and the boundary conditions linking medical students' rejection sensitivity to their problematic internet use, while also offering valuable practical implications for decreasing problematic internet use.