Breast cancer ranks among the most deadly gynecological cancers and presents a significant risk to women's health. Baicalein, a flavonoid extracted from Radix Scutellariae, has garnered significant interest due to its potential anti-cancer properties. However, further research is required to determine the precise anti-cancer mechanisms of baicalein. Hence, we investigated the anti-tumor properties and underlying mechanisms of baicalein in breast cancer, utilizing both network pharmacology and experimental approaches. The effects of baicalein on cellular proliferation, the cell cycle, and apoptosis were assessed through MTT assays, plate cloning, and flow cytometry techniques. Furthermore, network pharmacology was employed to identify the primary target and pathway associated with baicalein in the context of breast cancer. The validation of these target and the elucidation of baicalein anti-breast cancer mechanisms were carried out using Western blotting, qRT-PCR, molecular docking, CETSA assays, and IHC. Behavioral experiments were conducted to assess the physical changes and toxicity of baicalein in model mice. Our findings demonstrated that baicalein significantly reduced the growth of both MCF-7 and MDA-MB-231 cell lines in a dose-dependent manner, inhibited cell proliferation, induced G0/G1 phase arrest, and triggered apoptosis. Notably, SRC serves as a therapeutic target for baicalein, with the Hippo pathway identified as a crucial mechanism of action in this context. Intraperitoneal injection of baicalein has been demonstrated to effectively inhibit tumor growth, while concurrently ameliorating splenomegaly and enhancing the fatigue resistance of the model mice. The findings confirm that baicalein was a potential drug for the treatment of breast cancer.