To investigate the relationship between HLA-DQB1* alleles and major beta-thalassemia, the HLA-DQB1* loci typing was performed with polymerase chain reaction-sequence specific primer (PCR-SSP) in 42 unrelated (unconsanguineous) patients with major beta-thalassemia and 45 normal control individuals in Guangdong Province. Results showed that the frequency of HLA-DQB1*06 allele in patient group (19.0%) was higher than that in the control group (4.4%) kappa(2) = 8.961, p < 0.01). Our data suggests that HLA-DQB1*06 allele is associated with pathogenesis of the major beta-thalassemia in Guangdong area.