Baicalin is a flavonoid glycoside extracted from a kind of traditional Chinese drug, Scutellaria baicalensis, and possesses multiple pharmacological activities. The present study was designed to investigate the effects and mechanisms of baicalin against hepatic cancer cell growth and survival. We found that baicalin inhibited the viability and proliferation of two widely used hepatic cancer cell lines, Hep G2 and SMMC-7721 cells, in a dose-dependent manner. Cell cycle analysis revealed an increase in the S-phase cell population following 48 h exposure to baicalin. The expression levels of Cyclin A, CDK2, and Cyclin D1 were downregulated by baicalin treatment. Moreover, baicalin induced apoptotic cell death in Hep G2 and SMMC-7721 cells, which was accompanied by upregulation of Bax, downregulation of Bcl-2, and cleavages of Caspase-9, Caspase-3, and PARP. Furthermore, baicalin significantly inhibited the growth of xenografts in nude mice. In conclusion, we demonstrated for the first time that baicalin inhibited hepatic cancer cell growth and survival both in vitro and in vivo, suggesting that baicalin may be a potential phytochemical flavonoid for hepatic cancer therapy.