BACKGROUND Predisposing genetic factors in psoriasis include associations with human leukocyte antigen (HLA). Accumulative evidence has shown that certain HLA at class I locus, especially HLA-Cw6, are associated closely with psoriasis. OBJECTIVE To evaluate the association of HLA class I alleles with susceptibility to psoriasis in the southeastern Chinese Han population. METHODS We performed genotype for HLA-A, -B and -C loci in 166 patients with psoriasis vulgaris by means of polymerase chain reaction with sequence-specific primers technique. The distribution of HLA allelic frequencies was further analyzed according to age of onset, i.e. under 35-y and beyond 35-y groups. These data were compared with the healthy controls of 204 unrelated Hans. RESULTS The frequencies of HLA-A*26 (24.7% vs. 13.1%, OR=2.36, Pc<0.01), -B*13 (27.2% vs. 14.8%, OR=2.34, Pc<0.01), -B*27 (12.2% vs. 4.0%, OR=3.49, Pc<0.01) and -Cw*0602 (17.9% vs. 5.3%, OR=4.20, Pc<0.001) were significantly increased in psoriasis patients, whereas HLA-Cw*0304 frequency (4.9% vs. 13.4%, OR=0.32, Pc<0.01) was highly decreased, when compared to the controls. HLA-A*26-B*27-Cw*0602 was identified as a high-risk haplotype of HLA class I in developing psoriasis in the test. HLA-Cw*0602 was found to be strongly associated with the early-onset psoriasis (age of onset <35 y). CONCLUSIONS This study demonstrated the positive associations of HLA class I markers with psoriasis vulgaris, of which HLA-Cw*0602 was the strongest susceptibility determinant for development of early-onset psoriasis, in the southeastern Chinese Han population.