The root of Vitis labrusca, is used as a source of health promoting drug in Korean traditional medicine. It has been reported that root of Vitis labrusca has antioxidant, anti lipid peroxidation and anti-reactive nitrogen species (RNS) activities. The aim of this study was to elucidate the molecular changes of apoptotic signaling pathways in phorbol 12-myristate 13 acetate (PMA)-induced human hepatocellular carcinoma cell line (Hep G2). The root of Vitis labrusca, ethanol extract (RVLEE) was tested for cell viability on Hep G2 cell using the MTT assay. RVLEE exhibited weak cytotoxic activity. However, treatment of Hep G2 cells with RVLEE suppressed PMA-induced cell proliferation. Also, dramatic changes of cell death signals in cellular molecules such as Chk2/Cds1, CIDE-B, CLIMP-63, Bax, Bcl-xL, C-myc, Bcl-2, Bric-5, NIP-3, TRAF2 and BAR but not CIDE-B and DR4. Futhermore, our results showed that the treatment of Hep G2 cells with 25 and $50; {mu}g/ml$ of RVLEE suppressed PMA-induced COX-2 gene activity. These data suggest that RVLEE have inhibitory effect of cell proliferation, induction of apoptosis and, thus, may offer therapeutic potential in Hep G2.