Combined curcumin and PS-341 treatment has been reported to enhance cytotoxicity and minimize adverse effects through ERK and p38MAPK mechanisms in human multiple myeloma cells. However, whether JNK plays similar role in this process remains unclear. In the present study, we found combined treatment altered NF-kappa B p65 expressions and distributions in multiple myeloma H929 cells. Western blot analysis showed combined treatment inactivated NF-kappa B while activated JNK signaling. Pre-treatment with JNK inhibitor SP600125 could attenuate NF-kappa B inactivation and restored H929 cells' survival. These results suggested that curcumin might enhance the cytotoxicity of PS-341 by interacting with NF-kappa B, at least in part, through JNK mechanism.