Endemic nephropathy (EN) is a chronic tubulointerstitial kidney disease in which upper urothelial carcinoma (UUC) often occurs. The immune response and HLA genes have been linked with a number of diseases. Aim of this study was to analyze genes, alleles and haplotypes of HLA-A, -B and -DRB1 loci among EN patients (N=111; 52 patients with UUC and 59 patients without UUC) in order to investigate their possible role in EN etiology. In addition, analysis included 52 healthy relatives and 190 healthy unrelated individuals. HLA gene polymorphisms were determined by polymerase chain reaction methods in combination with oligonucleotides specific for HLA gene groups (PCR-SSO) or primers of specific sequences (PCR-SSP). Significant differences in distribution of several HLA alleles between EN patients and healthy controls were detected. The HLA-A*01:01, B*57:01 and B*27:05 alleles were significantly less present, while HLADRB1* 04:02 allele appeared significantly more frequently among EN patients. Positive corelation with the onset of EN and UUC was determined for HLAB* 18~DRB1*11 and HLA-B*44~DRB1*16 haplotypes, and HLAA* 26:01~B*38:01~DRB1*04:02 extended haplotype. Differences in distribution of alleles and haplotypes were also detected in correlation to age of disease onset and survival. Obtained data demonstrate that investigated HLA loci could be potential susceptibility/protection genetic markers for disesase development.