〔Abstract〕 Objective To investigate the effect and mechanism of puerarin on the proliferation, invasion and apoptosis of breast cancer cell HCC1806vianetwork pharmacology, molecular docking andin vitroexperiments. Methods The data of breast cancer and mitochondrial diseases were collected from GEO database, and the differentially expressed genes were analyzed by GEO2R. Overlapping genes between breast cancer and mitochondrial database were analyzed by Venn diagram. GO and KEGG enrichment analyzed the overlapping genes. STRING and Cytoscape analyzed overlapping gene interaction networks and screen core genes. Interaction between puerarin and core genes was docked with autodock. Cell proliferation, apoptosis and invasion capacity were measured by CCK-8, EdU, TUNEL and Transwell experiments, mitochondrial membrane potential was measured by Mito-Tracker experiments and protein expression levels were measured by Western blot. Anti-tumor efficacy of puerarin was analyzed by subcutaneous xenograft of breast cancer and immunohistochemical assayin vivo. Results Among 132 overlapping genes in breast cancer and mitochondrial disease, 10 core differentially expressed genes were selected. Among these core genes, dual serine/threonine and tyrosine protein kinase(DST) was low expressed in breast cancer tissues. Puerarin bound to DST, up-regulated its expression, inhibited the proliferation and invasion of HCC1806 breast cancer cells, promoted breast cell apoptosis, increased the expression levels of apoptosis-related proteins Cleaved-Caspase 3 and Bax, down-regulated the expression of anti-apoptosis protein Bcl-2, and decreased mitochondrial membrane potential.In vivo, puerarin inhibited the growth of breast cancer and up-regulated the expression of DST in tumor tissues. Conclusion Puerarin inhibits the proliferation and invasion of breast cancer cells, promotes the apoptosis of cancer cells and inhibits breast cancer growth.