Objective To analyze the human leukocyte antigen (HLA) gene polymorphism and haplotype frequency and distribution in Han patients with end stage renal disease (ESRD) in Sichuan province, and explore the correlation of HLA gene polymorphism and haplotype with the susceptibility to ESRD in Sichuan Han patients. Methods Polymerase chain reaction-sequence specific oligonucleotide probe hybridization typing technique was used to detect the HLA-A, -B, -DRB1, and -DQB1 genotypes of Han patients with ESRD and healthy participants. The allele and haplotype frequencies in the ESRD group and the control group were analyzed using SPSS 25.0 and Arlequin 3.5.2.2 softwares. Results A total of 756 ESRD patients and 1118 healthy participants were enrolled. In the four loci of HLA-A, -B, -DRB1, and -DQB1, the frequency of HLA-B*39 allele in the ESRD group was higher than that in the control group [3.37% vs. 2.19%; χ2=4.850, P=0.028, odds ratio (OR)=1.558, 95% confidence interval (CI) (1.047, 2.319)], the frequency of HLA-DQB1*06 allele in the ESRD group was lower than that in the control group [17.39% vs. 21.20%; χ2=8.264, P=0.004, OR=0.783, 95%CI (0.662, 0.925)], and the frequency of HLA-DQB1*04 allele in the ESRD group was higher than that in the control group [7.41% vs. 5.46%; χ2=5.867, P=0.015, OR=1.386, 95%CI (1.063, 1.807)]. The frequencies of 10 haplotypes, including HLA-A*11-B*39, HLA-DRB1*15-DQB1*06, and HLA-DRB1*04-DQB1*04, were significantly different between the ESRD group and the control group (P<0.05), among which 9 haplotypes were possibly susceptible to ESRD and 1 haplotype was possibly protective. Conclusions HLA gene polymorphism is closely related to the susceptibility to ESRD. HLA-B*39 and HLA-DQB1*04 may be susceptible genes for ESRD in Sichuan Han patients, while HLA-DQB1*06 may be a protective gene. In addition, 10 HLA haplotypes are possibly associated with the susceptibility to ESRD in Sichuan Han patients.