Abstract: Objective To observe the effects of Scutellaria barbata extract (ESB) on human hepatoma cell line Hep-G2 proliferation in vitro and explore the mechanism. Methods The inhibitory effect of ESB on Hep-G2 proliferation was estimated by MTT assay, and the morphological changes of the cells were observed under optical and electron microscopes. Distribution of cell cycle, cell apoptosis and the protein expressions of apoptosis-associated genes as bcl-2, bax and fas were analyzed using flow cytometry. Results ESB inhibited the proliferation of Hep-G2 cells in a time- and dose-dependent manner. ESB treatment for 72 h resulted in changes of early apoptotic morphology of the cells as observed under optical and the transmission electron microscopes and increased cell apoptosis. Cell cycle analysis revealed decreased S-phase and increased G0/G1-phase cells. Fas expression was significantly up-regulated in response to ESB treatment whereas Bcl-2 and Bax expressions underwent no significant changes. Conclusion ESB can inhibit Hep-G2 cell proliferation, induce cell cycle block, and increase cell apoptosis, which may relate to the activation of FNFR superfamily.