BackgroundPeer-mediated intervention (PMI) is an intervention that teaches normally developing peers to help children with autism spectrum disorder (ASD) actively participate in social interactions. Previous studies have shown that PMI applied to school settings is effective for children with ASD, but more multiple-baseline single-subject design. Many questions are still not clear due to the large clinical variability in children with ASD. This study investigated the effectiveness of PMI on social skills of children with ASD at varying symptom levels and analyzed the specific changes.MethodsThis study used a randomized, single-blind, parallel-controlled design to analyze the effect of PMI in a hospital setting. Fifty-five children aged 4–12 years were diagnosed with ASD by clinicians using the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and stratified randomly allocated to either the experimental group or the control group using the envelope method. The experimental group utilized PMI, whereas the control group utilized behavioral therapy based on applied behavior analysis (ABA) [early intensive behavioral intervention (EIBI)]. This study primarily utilized the Social Responsiveness Scale (SRS) to evaluate the social performance of autistic children prior to and after the intervention.ResultsFifty-five participants were recruited and analyzed, the experimental group (n=29; mild to moderate n=18, severe n=11) and the control group (n=26; mild to moderate n=15, severe n=11). After the intervention, the experimental group’s SRS score fell significantly more than the control group’s (t=−3.918, P=0.000), d=−1.043; the mild to moderate subgroup experienced the same situation (H=17.811, P=0.009), d=−1.642. At the same time, the decline in social communication scores was significantly greater in the experimental group compared to the control group (t=−3.869, P=0.000), and the 95% confidence interval was −10.067 to −3.193. The social motivation of the mild-to-moderate subgroup of the experimental group (H=16.894, P=0.011), −3.000 (25th percentile, 75th percentile: −3.000, 0.000), and the behavioral patterns of autism (H=18.150, P=0.006), −3.000 (25th percentile, 75th percentile: −5.000, 0.000), the decreased value was significantly larger.ConclusionsPMI therapy can increase social motivation in children with mild to moderate ASD, minimize undesirable behavior patterns, effectively improve overall social skills and enhance effective social communication with others.Trial RegistrationChinese Clinical Trial Registry ChiCTR2100049185.