The green tea constituent, (-)-epigallocatechin-3-gallate (EGCG), has chemopreventive and anticancer effects. This is partially because of the selective ability of EGCG to induce apoptosis and death in cancer cells without affecting normal cells. In the present study, the activity of EGCG against the myeloma cell line, KM3, was examined. Our results demonstrated, for the first time, that the treatment of the KM3 cell line with EGCG inhibits cell proliferation and induces apoptosis, and there is a synergistic effect when EGCG and bortezomib are combined. Further experiments showed that this effect involves the NF-kappaB pathway. EGCG inhibits the expression of the P65 mRNA and P65/pP65 protein, meanwhile it downregulates pIkappaBalpha expression and upregulates IkappaBalpha expression. EGCG also activates caspase-3, -8, cleaved caspase-9, and poly-ADP-ribose polymerase (PARP) and subsequent apoptosis. These findings provided experimental evidence for efficacy of EGCG alone or in combination with bortezomib in multiple myeloma therapy.