Playing critical roles in immune responses, interleukin-6 (IL-6) has been proposed to be involved in the development of multiple cancers, including prostate cancer. The rs1800795 polymorphism in the promoter of the gene IL-6 can affect the transcription and expression of the gene, becoming a common target in association studies on tumors. We therefore carried out this meta-analysis to further discuss the relationship of this polymorphism with the risk of prostate cancer.Relevant publications were retrieved from the electronic databases. The strength of the correlation between IL-6 rs1800795 polymorphism and prostate cancer risk was evaluated using pooled odds ratios (ORs) with their 95% confidence intervals (95% CIs). Q test was adopted to examine between-study heterogeneity, with P < 0.05 as significant level. Subgroup and meta-regression analyses were conducted to explore potential source of heterogeneity. Sensitivity analysis was implemented to test the statistical stability of the final results. In addition, funnel plot and Egger test were employed to inspect publication bias among included studies.A total of 13 132 cases and 15 282 controls were ultimately incorporated into the present study. Overall estimates revealed no significant relationship between IL-6 rs1800795 polymorphism and prostate cancer risk in total analysis, but a risk-increasing effect of the polymorphism was detected in African-American subgroup under CC versus GG and CC versus GG + GC contrasts (OR 3.43, 95% CI 1.01–11.71; OR 3.51, 95% CI 1.04–11.82) after subgroup analysis by ethnicity.IL-6 rs1800795 polymorphism may enhance the susceptibility to prostate cancer in African-American men.