Psoriasis is a chronic inflammatory disease with a strong genetic background, particularly the human leukocyte antigen (HLA). HLA-Cw6 has been shown to be the major disease susceptibility locus and affects the phenotypes and treatment response in psoriasis; however, the prevalence of HLA-Cw6 is far lower than HLA-Cw1 in some Asian countries. The aim of this study was to determine whether HLA-Cw1 predisposes psoriasis patients to different treatment responses of biologics and other systemic therapy. This retrospective case-control study included 126 patients with moderate to severe plaque-type psoriasis who had been genotyped and treated in a special psoriasis clinic. HLA-Cw1-positive and -negative patients were compared. Our results showed that HLA-Cw1-negative patients were significantly more likely to respond (achieve Psoriasis Area and Severity Index [PASI]75 after a 12- to 16-week treatment course) to biologics (including etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, and guselkumab; odds ratio [OR] 1.99, 95% confidence interval [CI] 1.17-3.44, p=0.0122) and especially to ustekinumab (OR 3.27, 95% CI 1.03-11.30; p=0.0496). An HLA-Cw1 allele dose effect was also found. The results remained after multivariate logistic regression analysis. HLA-Cw1-negative patients also showed significantly greater improvement of PASI in ustekinumab and biologics (p=0.0044 and p=0.0064, respectively), with other biologics showing non-significant trends. HLA-Cw1 status did not affect the treatment responses of non-biologic systemic treatment, including phototherapy. There is an association between HLA-Cw1 and treatment response to biologics, but not to non-biologics, in our Asian population of patients with moderate to severe psoriasis; however, the exact mechanism and role of HLA-Cw1 remain to be investigated.