Psoriasis is an inflammatory skin disease with a multifactorial genetic basis. A recent genome-wide association study identified several psoriasis-predisposing loci, including IL-12B, which encodes the common p40 subunit of interleukin (IL)-12 and IL-23 and the IL-23 receptor gene (IL-23R). To investigate the relationships of these predisposing polymorphisms with psoriasis in the Chinese Han population, we genotyped three representative variants (rs6887695, rs11465817, and rs1343152) in 217 unrelated patients and 288 control subjects using direct sequencing, We further replicated the positive polymorphism, rs6887695, in a larger combined sample that included 578 patients and 1422 controls. We found the single nucleotide polymorphism, rs6887695 (odds ratio = 1.33, 95% confidence interval 1.03-1.73, p = 0.028) of IL-2B to be significantly associated with psoriasis, and a novel halotype A-A of rs11465817-rs1343152 also showed a positive association. Our study confirms the effects of IL-12B and IL-23R variants on psoriasis in East Asian populations, and provides a reference point for further investigation of the role of the IL-12/IL-23 pathway in chronic epithelial inflammation in Asian and other ethnic populations.