To study the gene polymorphism of HLA-A, B, DRB1 alleles in patients with chronic myelogenous leukemia and to explore the correlation of HLA with chronic myelogenous leukemia, the polymerase chain reaction-reverse sequence specific oligonucleotide (PCR-RSSO) was used to analyze the polymorphism of HLA-A, B, DRB1 alleles of 293 CML Patients and 406 randomized and synchronous blood donors (healthy and unrelated with patients) from Guangdong Han population. The results indicate that the gene frequency of HLA-A*24 in CML group was 15.53% lower than that of control group (22.09%, RR = 0.63, p = 0.005); the gene frequency of HLA-B*13 in CML group was 10.41% higher than that of control group (6.74%, RR = 1.68, p = 0.016). The gene frequency of HLA- DRB1*14 in CML group was 7.51% lower than that of control group (11.89%, RR = 0.58, p = 0.008). The differences were all statistically significant. It is concluded that the gene frequency of HLA-A*24, HLA- DRB1*14 in CML patients is significantly lower than normal people in Guangdong. The gene frequency of HLA-B*13 in CML patients is significantly higher than normal people in Guangdong. Further study is needed to make sure whether HLA-A*24 and HLA- DRB1*14 are protective gene markers for CML acquisition on Guangdong Chinese Han population and whether HLA-B*13 is a gene marker for CML susceptibility on this population.