Salvia species have been used as valuable medicinal and herbal plant in many countries. Salvia officinalis L. and Salvia miltiorrhiza Bunge are widely used in traditional medicine for a long time. In the present study, cytotoxicity of ethanol and acetone extracts prepared from leaves and roots of two Salvia species was investigated using hepatocellular carcinoma cells (HepG2) and normal human liver cells (WRL-68). The cytotoxicity and anti-proliferative abilities of the extracts were evaluated by measuring cell viability (MTS assay), lactate dehydrogenase (LDH) leakage, the cellular ATP level, morphological changes using an inverted microscope, and apoptosis using flow cytometry. The results indicated that ethanol and acetone extracts of leaves and roots of S. officinalis (SO-L-E, SO-L-A, SO-R-E and SO-R-A, respectively) and ethanol and acetone extracts of roots of S. miltiorrhiza (SM-R-E and SM-R-A, respectively) significantly inhibited the proliferation of HepG2 cells in a time- and dose-dependent manner when the concentration was less than 150μg/mL. The cytotoxity of SO-L-E, SO-R-E and SO-R-A were significantly less in WRL-68 when compared to HepG2 cells in vitro. The increase of LDH leakage, decrease of ATP and the changes in morphology of HepG2 cells further confirmed the cytotoxic effect of these extracts to HepG2 cells. Furthermore, SO-L-E, SO-L-A, SO-R-E ethanol extract of leaves of S. miltiorrhiza (SM-L-E) and SM-R-E were able to induce apoptosis in HepG2 cells. This study shows the potential of the extracts to be used in the prevention and/or treatment of liver cancer or as ingredients in functional foods and provides scientific support for development and utilization of S. officinalis and S. miltiorrhiza, especially the roots of S. officinalis.