Background and Objective: Hepatocellular carcinoma (HCC) is a predominant type of Cancer in the liver than other cancers. World Health Organization predicted that the maximum mortality rate was caused by HCC (6th leading cause of death) and also by 2030, 1 million affected patients will die due to HCC. The molecular mechanism and treatment with plant-derived remedies/drugs giving better efficacy/resistance against HCC causing genes and its induced apoptosis. In the present (in vitro) study was designed to check the antitumor activity of the Chebulagic acid on HepG2 cells. Materials and Methods: Terminalia chebular derived Chebulagic acid anticancer activity on HepG2 cells was assessed by MTT assay, followed by DCFH-DA, Rhodamine123, acridine orange, Acridine orange/Ethidium bromide and DAPI fluorescent staining was done to check the apoptosis which was induced by Chebulagic acid on HepG2 cells. Results: The MTT assay revealed that Chebulagic acid treatment significantly inhibited cell proliferation and controlling ROS. Simultaneously, it shows a better effect on cells were pre-treatment with Chebulagic acid with dose and time-dependent based. Increased apoptotic cells (%) were found in mitochondrial membrane-associated and it's potential by Chebulagic acid on HepG2 cells. Conclusion: Overall findings of the study proposed that Chebulagic acid able to induce apoptosis HCC in human HepG2 cells by its apoptotic mechanisms.