Abstract: Objective　To analyze the relationship between HNF-4α gene polymorphism and non-alcoholic fatty liver disease (NAFLD). Methods　One hundred patients with NAFLD were selected as the observation group, and patients were divided into three subgroups according to the degree of disease: mild group (28 cases), moderate group (36 cases) and severe group (36 cases). One hundred healthy people for physical examination during the same period were selected as the control group. The general clinical data and blood biochemical indexes were compared between the two groups. The peripheral venous blood samples were collected from the two groups of patients, and the HNF-4α gene loci rs4812829 polymorphism was detected by polymerase chain reaction (PCR). The influencing factors of NAFLD was analyzed by Logistic regression analysis. Results　There were no significant differences in gender and age between the two groups (P＞0.05). The systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), waist-to-hip ratio (WHR) were significantly higher in the observation group than those of the control group (P＜0.05). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl transpeptidase (γ-GT), triglyceride (TG), total cholesterol (TC), low density liptein cholesterol (LDL-C), glucose (GLU), insulin resistance index (HOMA-IR) and uric acid (UA) levels generally showed an upward trend in the control group, mild group, moderate group and severe group (P＜0.05), while the high density lipoprotein cholesterol (HDL-C) level showed a downward trend (P＜0.05). There were no statistically significant differences in the distribution of HNF-4α rs4812829 allele and genotype between the observation group and the control group (P＞0.05). There were no statistically significant difference in the distribution of HNF-4α rs4812829 allele and genotype between different subgroups in the observation group (P＞0.05). There were no statistically significant differences in ALT, AST, γ-GT, TC, TG, HDL-C, LDL-C, GLU, HOMA-IR and UA levels between different genotype carriers at rs4812829 of HNF-4α in the observation group (P＞0.05). The risk of NAFLD in individuals with genotypes AG and AA was not increased compared with those in individuals with genotypes GG. Conclusion　The polymorphism and allele distribution of HNF-4α gene loci rs4812829 are not significantly related to the occurrence of NAFLD.