Objective: The interrelationships between cannabis use disorder (CUD), post-traumatic stress disorder (PTSD) and depressive symptoms, and non-suicidal self-injury (NSSI) were examined. Participants: Undergraduates (N = 363) who reported using cannabis within the past six months were recruited. Method: Mediation analyses was conducted to examine if CUD symptoms were indirectly associated with greater risk for engagement in current NSSI through more severe PTSD and depression symptoms. A factor comprised of PTSD-depression symptoms was created given PTSD and depression symptoms were highly correlated. Results: Greater CUD symptom severity indirectly increased risk for current NSSI via more severe PTSD-depression symptoms, after accounting for gender and alcohol use disorder symptoms. Conclusion: The current study provides preliminary evidence for the negative consequences of CUD on college students' mental health symptoms and engagement in NSSI, and future longitudinal research is needed to examine the dynamic relationships between CUD, PTSD-depression symptoms, and NSSI over time.