The impact of polysocial risk score (PsRS), a composite measure of multiple social risk factors, on the development of psoriasis remains unclear. Moreover, the potential modifying effects of lifestyle and genetic susceptibility on the relationship between PsRS and psoriasis risk require further exploration.This was a prospective cohort study conducted among UK Biobank.In this study, we analyzed 331,631 participants enrolled in the UK Biobank cohort. To derive the PsRS, we utilized a summative strategy, amalgamating six social determinants of health derived from three domains: socio-economic status, psychosocial factors, and neighborhood and living environment consistently linked to incident psoriasis. Cox proportional hazard models were used to assess the associations between PsRS and psoriasis incidence. Furthermore, we constructed a lifestyle score and a genetic risk score to explore the potential modifying effects of these factors on the relationship between PsRS and psoriasis risk.Compared with individuals with a low PsRS (≤1), those with intermediate PsRS (2-4) and high PsRS (≥5) had 1.20 (95% confidence interval [CI], 1.06-1.36) and 1.53 (95% CI, 1.31-1.78) times higher risks of developing psoriasis, respectively. Our findings revealed an additive interaction between PsRS and genetic susceptibility. Moreover, it was found that individuals with high PsRS and unhealthier lifestyles had a 2.60 times higher risk of developing psoriasis than those with lower PsRS and healthier ones.Our study results imply that an elevated PsRS is linked to a heightened risk of psoriasis, which is further influenced by genetic factors. Our results also indicate that greater social vulnerability and unhealthier lifestyle may synergistically contribute to the additional risk of psoriasis.Copyright © 2023 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.