Performed GO/KEGG enrichment analysis using the DAVID database; validated the binding potential between DEHP and core targets via molecular docking with AutoDock Vina; and finally verified the abnormal expression profiles of core targets through TCGA/GTEx transcriptomic data, HPA proteomic data, and RT-qPCR experiments in A-375 (human malignant melanoma cells)/Hacat cells.<h4>Results</h4>Initially, this study identified 11 key DEHP-induced skin cancer targets: CTNNB1, ESR1, HIF1A, IL6, MTOR, MYC, STAT3, AKT1, BCL2, CASP3, and CCND1. Here, HIF1A is linked to skin neoplasm.