// Tangyuheng Liu 1, * , Mei Zhang 1, * , Jiajia Song 1, * , Siyue Li 1, * , Jinya Zhang 1 , Xuejiao Hu 1 , Zhenzhen Zhao 1 , Wu Peng 1 , Qian Wu 1 , Hao Bai 1 , Yinyu Li 2 , Xiaojun Lu 1 and Binwu Ying 1 1 Department of Laboratory Medicine, West China Hospital, Sichuan University, Sichuan Province, P. R. China 2 Department of Laboratory Medicine, Affiliated Hospital of Chengdu University, Sichuan Province, P. R. China * These authors have contributed equally to this work Correspondence to: Xiaojun Lu, email: luxiaojun1972@163.com Binwu Ying, email: binwuying@126.com Keywords: HBV; IL-21; IL-21R; JAK/STAT; SNP Received: April 26, 2017 Accepted: December 27, 2017 Epub: January 02, 2018 ABSTRACT We investigated the relationship between hepatitis B virus (HBV)-related pathogenesis and single nucleotide polymorphisms (SNPs) in interleukin-21 (IL-21)-JAK-STAT signaling pathway genes. We used the high resolution melting (HRM) method to genotype five SNPs ( IL-21 rs2221903, IL-21 rs4833837, IL-21 receptor ( IL-21R ) rs2285452, JAK3 rs3008 and STAT3 rs1053023) in 546 HBV-infected patients and 353 healthy Chinese subjects. The HBV-infected patients were further divided into subgroups based on three HBV-related pathologies: chronic hepatitis B (CHB), liver cirrhosis and hepatocellular carcinoma (HCC). There were no significant differences in the genotype and allele distributions of the five SNPs between the HBV-infected patients and healthy subjects. However, patients with the IL-21R rs2285452 AA genotype were more susceptible to HBV-related HCC than those with the IL-21R rs2285452 GA/GG genotype (P = 0.03, OR = 3.27, 95% CI = 1.16-9.20). The HBsAg + HBeAg + anti-HBcAb + serological marker mode was predominant among the HBV-infected patients. However, there was no association between the genotype and allelic distribution of the five SNPs with any of the eight serological marker modes. These findings demonstrate that the IL-21R rs2285452 AA genotype increases the risk of HBV-related HCC in Chinese patients.