Background <p>Non-suicidal self-injury (NSSI) behavior represents a worrisome mental health concern across the world, with stressful life events emerging as a critical proximal predictor of NSSI behavior among college students. The high prevalence and severe implications of NSSI behavior necessitate a thorough investigation of the underlying mechanisms linking stressful life events to such maladaptive behavior among this vulnerable population.</p> Objective <p>This study aims to delineate the psychological pathways through which stressful life events contribute to NSSI behaviors among college students, with a focus on the sequential mediating roles of resilience and emotion dysregulation.</p> Methods <p>A cross-sectional convenience sample of 1,392 college students from Hunan Province, China, was recruited between September and December 2023. Data were collected via a structured online questionnaire, including the Ottawa Self-Injury Inventory (OSI), the Adolescent Self-Rating Life Events Checklist (ASLEC), the Difficulties in Emotion Regulation Scale (DERS), and the Resilience Scale for Chinese Adolescents (RSCA). Descriptive statistics, Pearson correlation analyses, hierarchical multiple regression analyses, and sequential mediation analysis were performed to evaluate the hypothesized relationships.</p> Results <p>The prevalence of NSSI behavior was 7.54% (105/1392), lower than reported in Western populations but consistent with some regional Chinese estimates. Between-group comparisons revealed that the NSSI group demonstrated elevated total scores and scores across all dimensions on the ASLEC (<i>p</i> &lt; 0.01) and DERS (<i>p</i> &lt; 0.01), while exhibiting lower total scores and scores across all dimensions on the RSCA (<i>p</i> &lt; 0.01). Correlation analysis indicated that NSSI behaviors were positively correlated with stressful life events (<i>r</i> = 0.408, <i>p</i> &lt; 0.01) and emotion dysregulation (<i>r</i> = 0.430, <i>p</i> &lt; 0.01), while negatively correlated with resilience (<i>r</i> = -0.592, <i>p</i> &lt; 0.01). Sequential mediation analysis revealed that resilience and emotion dysregulation jointly mediated the effect of stressful life events on NSSI behaviors, highlighting a nuanced interplay of protective and vulnerability factors.</p> Conclusion <p>These findings elucidate the intricate chain mediating effects of resilience and emotion dysregulation in the relationship between stressful life events and NSSI behaviors among college students. Given the cross-sectional design, causal inferences are constrained. Nonetheless, this study further provides valuable insights for the development and refinement of effective prevention strategies and intervention programs aimed at reducing NSSI risk.</p>