We investigated the effect of EPC-K1, which is a phosphodiester compound of vitamin E and vitamin C, on NF-κB activity in human cultured astrocytoma cells T98G. In TNFα-stimulated T98G cells, treatment with EPC-K1 inhibited both DNA binding activity and transactivation of NF-κB in a dose-dependent manner, and the suppressive effect of EPC-K1 was stronger than either that of vitamin E or vitamin C. Moreover, we showed that in TNFα-stimulated T98G cells treatment with EPC-K1 repressed NF-κB-dependent activation of the human immunodeficiency virus 1 promoter. In contrast, TNFα-induced activation of the human immunodeficiency virus 1 promoter was not completely inhibited by either treatment with vitamin E or vitamin C. We, thus, suggest that EPC-K1 is considered to be one of the inhibitory agents of NF-κB.