Abstract: Chelating ligand method has been used to synthesize baicalin-metal (Ni²⁺, Co²⁺, Cu²⁺) complexes (BMC). The composition and structure of BMC were characterized by the element analysis, ultraviolet spectrum (UV), infrared spectrum (IR), mass (MS) and thermal gravitational analysis (TGA). MTT was used to analyze the effects of BMC on SMMC-7721 cell proliferation. PI staining method and Annexin-V/FITC double staining method were used to analyze the effects of BMC on the cell cycle and apoptosis of SMMC-7721 cell. Fluorescence quantitative RT-PCR was used to analyze the expression of BMC on Bcl-2 gene and Bax mRNA, flow cytometry was used to analyze BMC on the expression of Bcl-2 protein and Bax protein. The antineoplastic activity and mechanism of action of BMC was explored comprehensively. The results showed that three new kinds of BMC (molar ratio of 2:1) were successfully prepared, the complexes molecular formula are: Na₂Ni(C₂₁H₁₆O₁₁)₂·10H₂O, Na₂Co(C₂₁H₁₆O₁₁)₂·8H₂O and Na₂Cu(C₂₁H₁₆O₁₁)₂·8H₂O. According to the results of cell cycle and apoptosis detection, BMC stopped cells at G₀/G₁ phase to S phase and G₂/M phase. Gene and protein detection showed that under the given concentration and time, BMC can downregulate the expression of Bcl-2 gene in SMMC-7721 cells, and significantly decrease the expression of Bcl-2 protein, at the same time, with the increase of expression of Bax gene, the Bax protein's expression increased significantly. Which indicates that BMC restrain cell proliferation and cell apoptosis by stopping cell cycle, reducing the expression of Bcl-2 and increasing that of Bax; The anti-tumor activities of three kinds of complexes were: baicalin-copper (BC-Cu) > baicalin-cobalt (BC-Co) > baicalin-nickel (BC-Ni) > baicalin (BC), showing the dose-response relationship.