OBJECTIVE To investigate the predisposing alleles of HLA-DRB1 genes in Han children with juvenile idiopathic arthritis (JIA) from Guangdong Province, China. METHODS Polymerase chain reaction-specific sequence primers (PCR-SSP) method was used to type HLA-DRB1 subregions in 94 Han children with JIA and 226 Han healthy controls. RESULTS The frequency of HLA-DRB1*08 allele in the JIA group was significantly higher than that in the control group (P=0.0014, OR=2.26), in contrast, the frequency of HLA-DRB1*12 allele was significantly lower than that in the control group (P=0.032, OR=0.55). It was found that in children with So-JIA subset (P=0.023, OR=2.25) and polyarthritis JIA subset (P=0.034, OR=2.81), the allele HLA-DRB1*08 was expressed most commonly. The allele HLA-DRB1*15 was expressed in a lower frequency in children with So-JIA subset (P=0.049, OR=0.413) and oligoarthritis subset (P=0.045, OR=0.16) compared with that in the control group. CONCLUSIONS HLA-DRB1*08 may be the susceptible allele of JIA, while HLA-DRB1*12 may be the protective allele of JIA in Han children from Guangdong Province. HLA-DRB1*08 is the susceptible allele of So-JIA and polyarthrits. HLA-DRB1*15 is the protective allele for systemic JIA and oligoarthritis.