Introduction: Genome wide association study has identified chromosome 6p21.33 as a risk locus of hepatocellular carcinoma (HCC). MiR-877 is located on this region, functioning as a tumor suppressor. The aim of this study was to investigate the association between rs1264440 in the promoter of miR-877 and HCC risk. Materials and methods: A total of 352 HCC patients and 359 age, gender, ethnicity and living area matched controls were enrolled in this study. The rs1264440 was genotyped using the TaqMan allelic discrimination assay. MiR-877 expression in HCC tissues was examined using quantitative PCR. Results: After Adjustment for age, sex, smoking status, drinking status and HBsAg status, this study showed a significant association between the rs1264440 and HCC risk. Subjects with the rs1264440 TT genotype and T allele showed a 2.20- and 1.44-fold increased risk to develop HCC, respectively (TT vs. CC: 95% CI, 1.18–4.11, P = 0.01; T vs. C: 95% CI, 1.07–1.94, P = 0.02). The increased risk was also observed in smokers and nondrinkers subgroup. The rs1264440 TT carriers had lower levels of miR-877. Conclusion: The rs1264440 in the promoter region of miR-877 may regulate miR-877 expression and serve as an independent biomarker for the risk of HCC. © 2020 Elsevier Masson SAS