Bisphenol F (BPF), a major alternative to bisphenol A (BPA), is now widely used worldwide, posing significant risks to human health and the environment. Acute myeloid leukemia (AML) is a highly aggressive hematologic malignancy with a poor prognosis. This investigation aims to systematically evaluate the potential hematotoxic of BPF in AML through an integrated computational biology approach combining network toxicology, molecular docking simulations and experimental validation. The study is designed to identify critical molecular targets and elucidate the mechanistic basis of BPF-mediated toxicity in AML. Using network toxicology and molecular docking techniques, we identified potential BPF targets through the SwissTargetPrediction, PharmMapper, and SEA databases. A total of 162 targets associated with BPF and AML were identified, with 25 key targets-including EGFR, ALB, BCL2, HSP90AA1, and ESR1-screened using STRING and Cytoscape tools. GO and KEGG enrichment analysis showed that "Pathways in cancer", "PI3K-Akt signaling pathway", "reactive oxygen species", "EGFR tyrosine kinase inhibitor resistance" and "Th17 cell differentiation" were mainly involved in potential toxicity of BPF in AML. Molecular docking with the CB-Dock online tool confirmed the stable interaction between BPF and key targets. Experimental validation supported these predictions: BPF exposure induced proliferation promotion in AML cell lines (HL-60/KG-1/MV4-11), along with rapid activation of EGFR/PI3K/AKT phosphorylation and BCL2 upregulation. In conclusion, this study provides a foundation for understanding the molecular mechanisms of potential toxicity of BPF in AML, provides valuable insights for risk assessment and public health policy, and emphasizes the need for stricter regulation and intervention of BPF exposure.Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.