Objective: To explore the relationship between the tumor necrosis factor receptor superfamily members 11A (TNFRSF11A) and 11B (TNFRSF11B) gene polymorphisms and the outcome of hepatitis C virus (HCV) infection. Methods: In this case-control study, 749 cases of persistent HCV infection, 494 cases of spontaneous clearance and 1 486 control subjects were included from 2008 to 2016. TaqMan-MGB probe method was used to detect the genotype of TNFRSF11A rs1805034 and TNFRSF11B rs2073617. The genotypes distribution of the two single nucleotide polymorphisms (SNP) were analyzed in different populations. Results: Co-dominant model showed that individuals carrying the rs2073617 CC genotype were prone to have chronic HCV infection, compared with individuals carrying the rs2073617 TT genotype (OR=1.517, 95%CI: 1.055-2.181, P=0.024). Recessive model results showed that individuals carrying rs2073617 CC genotype were more likely to develop chronic HCV infection compared with individuals carrying rs2073617 TT or TC genotype (OR=1.435, 95%CI: 1.033-1.996, P=0.032). Additive model showed that the risk for chronic HCV infection increased with the increase of the number of rs2073617 C alleles (OR=1.204, 95%CI: 1.013-1.431, P=0.035). Conclusion The genetic polymorphism of TNFRSF11B rs2073617 might be related with the chronicity of HCV infection.