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Hepatitis C virus (HCV) is a signifi cant health problem facing the world. More than million people are infected with HCV worldwide. HCV encodes a large polyprotein precursor that is processed into at least distinct products including structural (core, E and E) and non-structural (NS, NS, NSA, NSB, NSA and NSB). Besides its importance in virus replication, NSA functions as a cofactor for NS and contributes to viral pathogenesis by infl uencing cellular functions. Here, we investigated the eff ect of NSA protein on the growth rate induced by core protein in liver cells. Using our established tetracycline inducible system, we demonstrated the ability of NSA protein to inhibit core protein-in-duced cell growth in Hepatoma cell line, HepG. Induction of both core and NSA proteins in HepG-core/NSA transfectants inhibited core-induced growth advantage in HepG-core transfectants and blocked NSA protein-induced cell growth inhibition in HepG-NSA transfectants. Using both im-mune fl uorescence staining and Western blot analysis, we confi rmed the localization of NSA protein to the mitochondria in HepG-NSA transfectants expressing NSA protein. Data obtained from fl ow cytometry analysis, using JC- demonstrated the loss of mitochondrial membrane potential (ΔΨm) by the expression of NSA protein in HepG-NSA transfectants, but not by the expression of core protein in HepG-core transfectants. Whereas, the induction of the expression of both core and NSA proteins in HepG-core/NSA transfectants blocked NSA-induced loss of ΔΨm in HepG cells. Taken together, our data suggest an important role for mitochondria in the modulation HCV NSA-induced inhibition of HCV core-mediated cell growth