Adults of college age are at particular risk for psychopathology, non-suicidal self-injury (NSSI), and suicidal behavior, but protective factors (e.g., self-compassion) may buffer risk. We examined the mediating effect of NSSI on the relation between anxiety/depressive symptoms and suicide risk, and the moderating role of self-compassion. Students (N = 338) with greater psychopathology reported more engagement in NSSI and, consequently, more suicide risk; self-compassion weakened the psychopathology-NSSI linkage. Therapeutically addressing psychopathology and NSSI, perhaps via Cognitive Behavioral Therapy, and promoting self-compassion via compassion-focused and mindful self-compassion therapy, may halt progression from symptomology to self-harm, ultimately reducing suicide risk in college students.