Background <p>Borderline personality disorder is theorized to be the result of an interaction between biological vulnerability and an invalidating environment. Yet, few studies have investigated the relationship between these factors in adolescents with borderline personality features (BPF). The study examined the interactive effects of adolescents’ biological susceptibility and family invalidation on the severity of BPF.</p> Methods <p>Participants were 82 adolescents high in borderline personality features (high-BPF group) and 30 control adolescents (low-BPF group). Participants’ respiratory sinus arrhythmia (RSA) and skin conductance level (SCL) reactivity were monitored in a standardized Cyberball paradigm with simulated social stressor situations. They also reported perceived parental invalidation. Mixed-design ANOVAs were conducted to compare the physiological indicators between the groups in different conditions. Regression analyses were used to investigate the effects of biological susceptibility and invalidating family environment on the severity of BPF in adolescents.</p> Results <p>Results suggested that compared to the low-BPF group, the high-BPF group showed significantly greater RSA withdrawal after experiencing social exclusion. The effect of family invalidation on the severity of BPF was positively moderated by RSA reactivity.</p> Conclusions <p>Our findings highlight that adolescents with high BPF have higher levels of biological susceptibility to emotions, and family invalidation correlates with greater BPF severity only in adolescents who are more biologically sensitive to emotions. These findings offer valuable insights into the interactive effects of biological vulnerability and parental invalidation on BPF.</p>