AIM: To study the effects of hepatitis C virus (HCV) core and non-structural 5A (NS5A) proteins on nuclear factorκ B (NF- κ B) activity for understanding their biological function on chronic hepatitis caused by HCV infection.METHODS: Luciferase assay was used to measure the activity of NF- κ B in three different cell lines cotransfected with a series of deletion mutants of core protein alone or together with NS5A protein using pNF- κ B-Luc as a reporter plasmid. Western blot and indirect immunofluorescence assays were used to confirm the expression of proteins and to detect their subcellular localization, respectively.Furthermore, Western blot was also used to detect the expression levels of NF- κ B/p65, NF- κ B/p50, and inhibitor κ B-a(I κ B-a).RESULTS: The wild-type core protein (C191) and its mutant segments (C173 and C158) could activate NF- κ B in Huh7 cells only and activation caused by (C191) could be enhanced by NS5A protein. Moreover, the full-length core protein and its different deletion mutants alone or together with NS5A protein did not enhance the expression level of NF- κ B. The NF- κ B activity was augmented due to the dissociation of NF- κ B-I κ B complex and the degradation of Iκ B-a.CONCLUSION:NF- κ B is the key transcription factor that can activate many genes that are involved in the cellular immune response and inflammation. Coexpression of the full-length core protein along with NS5A can enhance the NF- κ B activation, and this activation may play a significant role in chronic liver diseases including hepatocellular carcinoma associated with HCV infection.