Background:The genes that encode the human leukocyte antigens (HLA) molecules are the most polymorphic in the human genome and have been considered as possible genetic risk factor in the development of acute and chronic leukemias. Objective: This study aimed at evaluating the role of HLA DRB1 alleles as markers for selection of the line of therapy in Acute myeloid leukemia (AML) and Chronic myeloid leukemia (CML) patients. Methodology: The study was conducted on: 20 AML, 20 CML cases and 20 healthy controls. Typing was done by the sequence-specific primer (PCR-SSP). Results: There was a highly statistical significance association between response to treatment and HLA DRB1 alleles as markers (MCP= .0001) in AML and CML patients. The HLA-DRB1 04*04 allele was found to be associated with good response to therapy in AML patients while, HLA-DRB1 07*15 allele was associated with bad response. In CML patients, HLA-DRB1 03*11 allele was found to be associated with good response to therapy while, HLA-DRB1 alleles 03*04 and 11*15 alleles were equally associated with bad response. Conclusion: Future researches are mandatory especially on larger scale to confirm whether these alleles are protective or even risk alleles regarding both AML and CML.