Objective: To explore the relationship of self-injurious behavior with peer discrimination and depression among AIDS orphans, so as to provide the basis for promoting the mental health of AIDS orphans. Methods: From March 2021 to March 2022, 626 AIDS orphans from 5 counties in Henan Province were selected by stratified cluster random sampling methods. Non suicidal Self-injury assessment Tool, Discrimination Experience Scale, and Zung Self-rating Depression Scale were used to investigate AIDS orphans self-injurious behavior, peer discrimination and depression. Multivariate Logistic regression model was used to analyze the relationship between self-injurious behavior and peer discrimination of AIDS orphans. Multivariate linear regression analysis was used to explore the moderating effect of depression between self-injurious behavior and peer discrimination of AIDS orphans. Results: The detection rates of self-injurious behavior, peer discrimination and depression of AIDS orphans were 80.0%, 73.3% and 67.6 % respectively. The detection rates of the three items mentioned above were 86.9%, 81.5%, and 77.5% for double orphaned children, respectively, which were higher than 74.6%, 67.0%, and 59.8% for single orphaned children, and the differences were statistically significant ( χ 2=21.29, 23.78, 14.23, P <0.01). The score of self-injurious behavior of AIDS orphans was positively correlated with peer discrimination and depression ( r=0.55, 0.40, P <0.01). Depression played a moderating role in the relationship between self-injurious behavior and peer discrimination of AIDS orphans ( β= 0.03, P <0.05). Conclusions AIDS orphans are more likely to engage in self-injurious behaviors after experiencing peer discrimination and psychological depression. The society and schools should adopt targeted intervention strategies to promote the mental health among AIDS orphans.