Abstract Background Psoriasis is a systemic immune disease associated with the development of various cancers. However, the causal nature of
Abstract Background Psoriasis is a systemic immune disease associated with the development of various cancers. However, the causal nature of this association remains unclear. This study aims to systematically investigate the potential causal relationship between psoriasis and 32 types of cancer. Methods We utilized data from two large genomic databases, the UK Biobank and FinnGen, to extract GWAS summary statistics for 32 cancer types as outcomes and psoriasis-related data as exposures. Mendelian randomization (MR) analysis was performed to assess the causal effects of psoriasis on cancer risk. Sensitivity analyses, including heterogeneity and horizontal pleiotropy tests, were conducted to ensure robustness. Additionally, meta-analysis and FDR correction were applied to enhance the reliability of the results. Results Our findings revealed significant causal relationships between psoriasis and four cancer types: Psoriasis was associated with an increased risk of laryngeal cancer (OR = 1.15, 95% CI: 1.05–1.26). Psoriasis exhibited a protective effect against oral cavity and pharyngeal cancer (OR: 0.91; 95% CI: 0.86–0.97), prostate cancer (OR: 0.97; 95% CI: 0.95–0.99), and malignant non-melanoma cancer (OR: 0.89; 95% CI: 0.82–0.96). Conclusion Psoriasis may exert bidirectional effects on the development of specific cancers through distinct mechanisms. Specifically, psoriasis may increase the risk of laryngeal cancer while reducing the risk of oral cavity and pharyngeal cancer, prostate cancer, and malignant non-melanoma cancer. These findings provide new insights into the causal relationship between psoriasis and cancer and could inform prevention and treatment strategies for these diseases.