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The estrogen receptor β (ESR-β) gene is suggested to have a growth-inhibiting role in prostate tissue and has been proposed as a new treatment to target prostate cancer (PCa). Previous studies have investigated the association between the ESR-β rs1256049 polymorphism and PCa, but findings have been inconsistent. Thus, this meta-analysis was performed to assess whether the ESR-β rs1256049 polymorphism is associated with an increased susceptibility to PCa. Eligible studies published before February 5, 2022 were systematically searched for in the PubMed, Web of Science, ScienceDirect and Google Scholar databases. The sample set was extracted from 11 case-control studies involving 9,390 cases and 10,057 controls on the link between ESR-β rs1256049 polymorphism and PCa susceptibility. In our overall meta-analysis, no significant link between rs1256049 and PCa risk was found under all genetic models. In subgroup analysis according to ethnicity, those of Asian origin had a significantly decreased cancer risk based on both the heterozygote genetic model (OR = 0.75, 95% CI = [0.63, 0.89] P = 0.01) and the dominant model (OR = 0.80, 95% CI [0.69, 0.94] P = 0.01). For the Caucasian group, there was a significantly increased risk observed in the allelic model (OR = 1.17, 95% CI = [1.04, 1.32] P = 0.01), heterozygote model (OR = 1.15, 95% CI = [1.01, 1.31] P = 0.03), and the dominant model (OR = 1.17, 95% CI = [1.03, 1.32] P = 0.01). Our results demonstrate that ESR-β r1256049 polymorphism may play a possible effect in PCa development in Caucasians and be a protective factor in Asians.