ABSTRACT: Cerebral palsy (CP) is a kind of movement and posture disorder syndrome in early childhood. In recent years, human mesenchymal stem cell (hMSC) transplantation has become a promising therapeutic strategy for CP. However, clinical evidence is still limited and controversial about clinical efficacy of hMSC therapy for CP. Our aim is to evaluate the efficacy and safety of hMSC transplantation for children with CP using a meta-analysis of randomized controlled trials (RCTs). We conducted a systematic literature search including Embase, PubMed, ClinicalTrials.gov, Cochrane Controlled Trials Register databases, Chinese Clinical Trial Registry, and Web of Science from building database to February 2020. We used Cochrane bias risk assessment for the included studies. The result of pooled analysis showed that hMSC therapy significantly increased gross motor function measure (GMFM) scores (standardized mean difference (SMD) = 1.10, 95%CI = 0.66-1.53, P < 0.00001, high-quality evidence) and comprehensive function assessment (CFA) (SMD = 1.30, 95%CI = 0.71-1.90, P < 0.0001, high-quality evidence) in children with CP, compared with the control group. In the subgroup analysis, the results showed that hMSC therapy significantly increased GMFM scores of 3, 6, and 12 months and CFA of 3, 6, and 12 months. Adverse event (AE) of upper respiratory infection, diarrhea, and constipation was not statistically significant between the two groups. This meta-analysis synthesized the primary outcomes and suggested that hMSC therapy is beneficial, effective, and safe in improving GMFM scores and CFA scores in children with CP. In addition, subgroup analysis showed that hMSC therapy has a lasting positive benefit for CP in 3, 6, and 12 months.