Network pharmacology analysis identified multiple targets of isoliquiritigenin related to breast cancer, with epidermal growth factor receptor (EGFR) as one of the key hub. Molecular docking indicated a stronger binding affinity of isoliquiritigenin compared to ATP, while molecular dynamics simulations confirmed the stability of the EGFR–isoliquiritigenin complex with binding free energy estimated at − 30.002 ± 3.879 kcal/mol. This evidence concerns the gene EGFR and breast carcinoma.