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Non-Suicidal Self-Injury in Autism Spectrum Disorder: A Systematic Review of Associated Factors and Management Difficulties Background: Non-suicidal self-injury (NSSI) is defined as the intentional damage to one’s body tissue without suicidal intent and for reasons that are not socially sanctioned. While NSSI has been widely studied in the general population, its clinical correlates and management in autism spectrum disorder (ASD) remain less clearly characterized, and it is often conflated with self-injurious behavior (SIB) described within restricted and repetitive behaviors (RRBs). In individuals with ASD, NSSI may be associated with emotional, behavioral, cognitive, social, medical, and demographic factors, and it differs from SIB typically observed among individuals with severe intellectual disabilities. Methods: A systematic review was conducted in accordance with PRISMA guidelines. Studies published between 2000 and 2025 that assessed NSSI in individuals with a formal ASD diagnosis were included. Etiological/clinical correlates, explanatory mechanisms, and management challenges were examined. Sixteen studies were selected from PubMed, Scopus, and Web of Science. Findings were synthesized using narrative and thematic approaches. Results: The prevalence of NSSI among individuals with ASD ranged from 24% to 50%. Associated factors included emotion dysregulation (including alexithymia and affective distress), behavioral dysregulation (e.g., impulsivity/hyperactivity and aggression), sensory processing difficulties, communication and social impairments, and medical comorbidities (i.e., gastrointestinal and sleep problems), with preliminary evidence also implicating perinatal factors. NSSI was linked to emotion regulation, sensation seeking, and social communication processes. Early intervention and parental involvement were identified as protective factors. Conclusions: NSSI in ASD is a complex, multifactorial phenomenon frequently linked to emotion-regulation needs. Affective imbalance represents a central—though not exclusive—pathway. The review supports standardized terminology, function-based assessment, and clearer differentiation from SIB/RRBs, with implications for individualized interventions and sustained monitoring in persistent or severe cases. Routine screening for medical and sensory contributors may further improve case management and reduce preventable clinical burden. https://doi.org/10.3390/jcm15031254