Abstract Background：The association of ABO blood groups with epithelial ovarian cancer (EOC) risk has been reported. However, the results are inconsistent and little is known about the alterations of histo-blood group antigens expression and ABO gene expression in ovarian tumor tissues. Methods：We used two single nucleotide polymorphisms in ABO gene (rs8176719 and rs8176746) to determine ABO blood group of 1,870 EOC cases and 4,829 controls. Expression of A and B antigen in 70 ovarian tumor tissues and adjacent normal tissues were detected by immunohistochemistry. Gene expression and DNA methylation profiling was detected in ovarian tumor tissues.Results：In this case-control study, blood group A was associated with increased risk for EOC compared with blood group O (OR = 1.18, 95 % CI = 1.03 – 1.36, P = 0.019), this association remained significant after multivariate adjustment (adjusted OR = 1.48, 95% CI= 1.11 – 1.96, P = 0.007). Patients with blood group A had higher rate of aberrant histo-blood group antigen expression compared to patients with blood group O and B (76.5% vs. 21.1%, 5.0%, P<0.001). ABO gene expression was down-regulated in ovarian tumor tissues compared with paired adjacent normal tissues (P = 0.027). NFYB was positively correlated with ABO gene expression (r = 0.38, P<0.001) and DNA methylation level of four CpG sites was significantly inversely correlated with ABO gene expression (cg11879188, r = - 0.3, P = 0.002; cg22535403, r = - 0.30, P = 0.002; cg13506600, r = - 0.22, P = 0.025; cg07241568, r = - 0.21, P = 0.049). Conclusions：We identified blood group A was associated with increased EOC risk in Chinese women and provided the clues of the possible molecular mechanisms of blood group A related to ovarian cancer risk. Functional studies are warrant to clarify the role of A antigen and ABO gene in ovarian cancer carcinogenesis.