Background: Schizophrenia is a complex brain disorder, the pathogenesis of which remains unclear.Regulator of G-protein signaling 4 ( RGS4 ) is regarded as a candidate gene for schizophrenia risk. The association between the RGS4 gene and the risk of schizophrenia is complicated and controversial, thus, an updated meta-analysis is needed. Methods: A search strategy using Medical Subject Headings was developed in English (PubMed, SZGene) and Chinese (CNKI, Wanfang and Weipu) databases. Inclusion and exclusion criteria were used to screen for eligible studies. Parameters, such as P -value of Hardy − Weinberg equilibrium ( P HWE ), odds ratios (ORs), 95% confidence intervals (CIs), P -values of association ( P z ,), heterogeneity ( P h ), and publication bias ( P e ), were analyzed by the Stata software using a random effects model. Subgroup analyses were performed to detect heterogeneity. Results: There were 15 articles regarding rs10917670 (8,046 cases and 8,837 controls), 16 regarding rs951436 (8,990 cases and 10,568 controls), 15 regarding rs951439 (7,995 cases and 8,646 controls), 15 regarding rs2661319 (8,320 cases and 9,440 controls), and 4 regarding rs10759 (2,752 cases and 2,866 controls). The frequencies of rs10917670 and rs951439 were not significantly different between the case and control groups (p > 0.05). As shown by the East Asian and hospital-based subgroup analyses, the genotype TT of rs951436 might be related to the risk of schizophrenia. The genotypes CC+CT of rs2661319 and CC+CA of rs10759 were statistically different between the two groups, and the East Asian population contributed to these differences. Conclusion:The genotypes CC+CT of rs2661319 and CC+CA of rs10759 might be associated with the risk of schizophrenia.