This study investigated the protective potential of Naringin (NIN) against cadmium chloride (CdCl ) mediated hepatotoxicity using human hepatocellular carcinoma (HepG2) cells. An optimal concentration of NIN (5 μM) was potent enough to confer cytoprotection against CdCl (50 μM) as was observed by MTT assay. Preconditioning with NIN maintained redox homeostasis, mitochondrial membrane potential, and reduced apoptosis as marked by decrease in the percentage sub-G /G and Annexin V-FITC/propidium iodide positive cells (apoptotic). NIN pretreatment maintained the levels of protein thiol along with endogenous activities of Superoxide dismutase, Glutathione S-transferase, and Catalase and lowered lipid peroxidation. Decreased Bax/Bcl2 ratio along with reduced Caspase 3 cleavage and Cytochrome c release indicated that NIN conditioning blocked mitochondrial-mediated apoptosis. Increased Nrf2 and metallothionein (MT) acted as adaptive response in the presence of cadmium. Thus, the protective mechanism of NIN is attributed to its antioxidant potential which aids in redox homeostasis and prevents CdCl mediated cytotoxicity.