Objective To investigate the anti-tumor activity of total glycoside of Cimicifuga foetida L.（TGC） and its mechanism. Methods The growth inhibitory effect of TGC on human hepatoma cell line HepG2 was observed by using assay（MTT）；In vivo anti-tumor activity of TGC were evaluated in transplant hepatoma H22 model and human hepatocellular carcinoma Bel-7402 xenograft nude mice model；Cell cycle distribution was assayed by flow cytometry. Results TGC could markedly inhibit the growth of HepG2 （IC50=76.16±2.94 mg·L-1）. Compared with the solvent group，TGC showed a significant inhibitory effect on H22 and Bel-7402 at a dose of 0.8 g·kg-1. Furthermore，TGC could arrest HepG2 at G2/M phase at a concentration of 50 mg·L-1 in a time-dependent manner. Conclusion TGC had significant anti-tumor effects both in vivo and in vitro，which might be associated with the arresting of the tumor cell cycle at G2/M phase.