We explore the association of Malassezia and IL-23/IL-17 axis in the skin lesions of patients with Psoriasis. From October 2018 to October 2020, 202 psoriasis patients were hospitalized in the dermatology department of Yantaishan hospital. The patients' skin lesions were collected, and Malassezia-specific mRNA in the skin lesions was determined. The patients were subdivided into Malassezia high and low distribution groups as per the Malassezia-specific mRNA results. Psoriasis Area and Severity Index (PASI) scores between the two groups were performed. LL-37, IL-23, IL-17A, and tumor necrosis factor alpha (TNF-alpha) expression in the skin lesions of the two groups were determined. Malassezia mRNA and the correlation of LL-37 with inflammatory factors TNF-alpha, IL-23, and IL-17A were determined. The relevance of inflammatory factors, Malassezia infection, and LL-37 content with PASI score were studied. The Malassezia high distribution group was treated with ketoconazole, and the effects of treatment on the PASI score, IL-23, TNF-alpha, and IL-17A were determined. The PASI score, neutrophil, eosinophil, and peripheral blood white blood cell counts, and lgG in the Malassezia high distribution group were significantly higher than in the low distribution group (P < 0.05). IL-23, LL-37, TNF-alpha, and IL-17A levels in the Malassezia high distribution group were significantly higher than in the low distribution group (P < 0.05). Malassezia and LL-37 levels had a moderate positive correlation (R=0.5009, P < 0.0001). Malassezia and LL-37, IL-17A, TNF-alpha, and IL-23 correlated positively. Malassezia, IL-17A, LL37, TNF-alpha, and IL-23 correlated positively with the PASI score of Psoriasis. Ketoconazole therapy inhibited the PASI score, IL-23, TNF-alpha, and IL-17A expressions in patients. Malassezia enhances the progression of Psoriasis through the aberrant activation of the IL-23/IL-17 axis.