Introdution: Hepatocellular carcinoma (HCC) is one of the most common cancers. It is the third leading cause of cancer related death. This study aimed to evaluate the phytochemical composition of ethanolic and aqueous Glycyrrhiza glabra root extracts its apoptotic effects against human hepatocarcinoma HepG2 cell line. Methods: In the current experimental study, the phyochemical composition of aqueous and ethanolic Glycyrrhiza glabra extract was evaluated by GC/MS method. The HepG2 cells were grown in RPMI1640 supplemented with 10 % (v/v) FBS at 37°C with 5 %carbon dioxide (CO2) atmosphere. The cytotoxicity activities of extracts were measured using MTT after 24 hours. To evaluate the ability of extracts to trigger apoptosis in HepG2 cells, the Hosest8778 staining method was carried out. Results: The phytochemical data of aqueous extract revealed 18 compounds, including Dodecane (13.34%) and 2',6'-Dihydroxyacetophenone bis (trimethylsilyl) ether (12.48%) as the major constitutes. The chemical composition of ethanolic extract showed 17 compounds, including Pentadecane (7.78%), 2,6,11,15-Tetramethylhexadecane (4.67%) as the prominent compounds. The MTT results revealed that the extract-treated cells had a dose-related toxicity effects. The results of Hoechst 33258 staining showed that the nuclear DNA fragmentation was increased in the ethanolic extract treatment compared to aqueous extract. Conclusion: The ethanolic extract of Glycyrrhiza glabra possesses more apoptotic effect on cancer cells and further researches are needed for investigating its potential mechanism