Deliberate self-harm is not only a major global public health problem but also an important index of psychological distress and a risk factor for suicide. We aimed to determine the psychosocial risk factors for deliberate self-harm in patients aged ≥ 16 years presenting to tertiary care hospitals in Kabul, Afghanistan. A matched case-control study was conducted from February 2015 to May 2015. We recruited 185 cases (patients with deliberate self-harm) and 555 age- and sex-matched controls (patients with general medical conditions) from 4 tertiary care hospitals in Kabul. We developed a questionnaire to record the sociodemographic characteristics of the participants, history of domestic violence, drug abuse and details about the act of deliberate self-harm, including the methods used. To assess depression and anxiety, we used the WHO self-reporting questionnaire (SRQ-20). Matched odds ratios with 95% confidence interval using conditional logistic regression were used to determine statistically significant associations between psychosocial factors and deliberate self-harm. Family conflicts, domestic violence, interpersonal arguments and living in extended families were found to be significantly associated with deliberate self-harm. In Afghanistan, deliberate self-harm appears to be predominately related to interpersonal problems and family conflicts. About two-thirds of females and more than half of males scored positive for depression, yet none were receiving treatment for this. These findings have important policy implications for mental health and suicide prevention programmes in the country.