Background: Psoriasis is a multifactorial, chronic immunological disease, in which a specific allele HLA-Cw6 is associated with various clinical manifestations. However, information regarding this genetic factor in Korean patients with psoriasis remains limited. Objective: We aimed to explore the differences in clinical patterns and treatment responsiveness, depending on the expression of HLA-Cw6, in Korean patients with psoriasis. Methods: We divided patients into two groups, namely HLA-Cw6-positive and HLACw6-negative, based on the HLA-Cw6 allelic analysis using the single specific primerpolymerase chain reaction method. All clinical information regarding these patients was collected in a retrospective manner. Next, we evaluated the levels of serum Th17-related cytokines in 34 patients diagnosed with psoriasis using a multiplex immunoassay. Finally, we performed immunohistochemical staining of interleukin (IL)-22 and IL-31, as these cytokines showed the maximum differential expression between the HLA-Cw6 positive and negative groups. Results: HLA-Cw6 positive and negative groups comprised of 13 and 21 patients, respectively. HLA-Cw6-positive group had more chance of having metabolic comorbidities (76.9% for HLA-Cw6-positive group; 28.6% for HLA-Cw6-negative group; p=0.002). Also, HLA-Cw6-positive group showed significantly higher treatment response (38.5% in positive group showed Psoriasis Area and Severity Index 90% improvement compared to 4.8% in the negative group; p=0.012). However, all Th17-related cytokines were not significantly different across the two groups. Furthermore, IL-22 and IL-31 immunohistochemical staining did not correlate with the serum cytokines levels. Conclusion HLA-Cw6 types can be associated with disease severity, comorbidities, and treatment responsiveness in Korean patients with psoriasis.