Objectives: To analyze the effect of human placental extracts (HPEx) on hepatocellular carcinoma cells in vitro. Methods: The hepatocellular carcinoma cell lines, namely, HLE and Huh-7, were used. The cells were subjected to a growth assay using the formazan dye method; the effect of combination treatment with sorafenib and HPEx was also assessed. The preventing normal cell damage effect of HPEx was analyzed by virtual therapy where possible; the experimental protocol was constructed on the basis of pre- and post-sorafenib treatment data. Cytotoxicity was measured by lactate dehydrogenase (LDH) assay. Results: HPEx caused significant dose-dependent suppression in the growth of HLE and Huh-7 cells. These tumor cells were significantly suppressed by combination treatment with HPEx and sorafenib. In addition, HPEx potentiated sorafenib sensitivity against tumor cells, and significantly prevented sorafenib-induced cytotoxicity in primary cultured rat hepatocytes under all designed experimental conditions. Specifically, pre-treatment with HPEx had a greater effect than post-treatment with HPEx. Conclusion: HPEx suppresses tumor cell growth, potentiates sorafenib efficacy, and has a preventing normal cell damage effect; this triple functionality of HPEx makes it a useful agent for liver cancer therapy.