Background: Human leukocyte antigens (HLAs) are found to be significant genetic factors concerning the susceptibility of an individual to certain diseases. Objective: To determine the association between variants of class I (A and B) and class II (DRB1) HLA alleles and chronic renal failure (CRF), compared with healthy controls, in Yemen. Methods: A case-control study in the Urology and Nephrology Center at Al-Thawra University Hospital in Sana’a, Yemen was carried out between January 2013 and December 2015 and included 187 CRF patients, and 194 healthy controls visiting the same center for kidney donation. All CRF patients in the study were on haemodialysis. The control group was confirmed to be healthy following a clinical examination by specialist physicians. Among both patients and controls, HLA class I (A and B) and class II (DRB1) HLA typing was carried out by Sequence Specific Primers (SSP) polymerase chain reaction (PCR). Results: There was a significant protective function for HLA-A*30 gene (CRF 9.1% vs. con 16%, p=0.045) against CRF development. There was a high frequency of HLA-A*02, HLA-B*51 and HLA-DRB1*04 alleles in both patients and controls. Conclusion: No HLAs were located to have a significant association with genetic tendency to CRF in the current study population, however, certain HLA alleles, for instance in HLA-A*30, could be considered protective against CRF progress.