Arecoline, the major alkaloid of areca nut, is a common exposure in chewing products, but its relationship with prostate cancer (PCa) is unclear. We integrated network toxicology, bulk RNA machine learning, single-cell transcriptomics, molecular simulation, and in vitro validation to prioritize candidate molecular nodes potentially linking arecoline exposure to PCa-related alterations. Potential arecoline targets were intersected with PCa-related genes, followed by protein–protein interaction an