Several studies have evaluated the possible association between polymorphisms or variants in Corticotropin-releasing hormone 1 receptor gene (CRHR1) with depression; however, results remain contradictory and heterogeneous.To our knowledge, we conducted the first comprehensive systematic review and meta-analysis evaluating the association of the CRHR1 gene and the risk of depression.A search online was conducted in databases for any CRHR1 genetic association studies in depression. Data were extracted for evaluation of pooled estimates using meta-analytic techniques. Statistical analyses were performed using the Comprehensive Meta-analysis, v2.0 software.A total of 1403 cases and 2353 mentally healthy controls were included in this study. We found a significant association of rs242941, rs1876828 and rs242939 variants of the CRHR1 gene with depression. No association of CRHR1 rs110402 and depression was observed.Our meta-analysis shows that some variants of the CRHR1 gene (rs242941, rs1876828 and rs242939) might confer susceptibility to depression. Further studies with larger sample sizes need to be conducted.