Résumé : Aims: To test, among Chinese adolescents: (1) whether childhood maltreatment is associated with non-medical use of prescription drugs (NMUPD) and (2) whether there are interaction effects of childhood maltreatment and depressive symptoms on NMUPD. Design: A secondary analysis of the cross-sectional data collected from 7th- and 12th-graders who were sampled using a multi-stage, stratified-cluster, random-sampling method in the 2015 School-based Chinese Adolescents Health Survey (SCAHS). Setting: Surveys conducted in high schools in six cities of China in 2015. Participants: There were 24 457 students who were invited to participate and 23 039 students’ questionnaires were completed and qualified for our survey. Measurements: The outcomes comprised self-report of NMUPD (prior 30 days); a history of childhood maltreatment was our main predictor. Other covariates included depressive symptoms, smoking, drinking and demographics. Data were analysed using multi-level regression modelling. Findings: Our final multivariable logistic regression models demonstrated that after adjusting for other variables, physical abuse was associated positively with non-medical use of opioids [adjusted odds ratio (AOR) = 1.13, 95% confidence interval (CI) = 1.10–1.22], sedatives (AOR = 1.11, 95% CI = 1.10–1.21) and any prescription drugs (AOR = 1.13, 95% CI = 1.09–1.20); emotional abuse, sexual abuse and emotional neglect were also associated with an increased risk of opioids, sedatives and any prescription drugs misuse; students who reported that they had experienced childhood physical neglect were more likely to be involved in the non-medical use of sedatives (AOR = 1.08, 95% CI = 1.04–1.12) and any prescription drugs (AOR = 1.06, 95% CI = 1.03–1.10). Additionally, there was no evidence of interaction effects on NMUPD between depressive symptoms and each of physical abuse, emotional abuse, sexual abuse, physical neglect and emotional neglect, respectively. Conclusions: Maltreatment while a child is associated with an increased risk of non-medical use of prescription drugs (NMUPD) among Chinese adolescents. The interactions of maltreatment while a child and depressive symptoms do not appear to be associated significantly with NMUPD among Chinese adolescents.