NKILA is down-regulated in HCC and reduced expression of NKILA indicts poor survival of HCC patients. Overexpression of NKILA enhances the roles of baicalein on HCC cell proliferation inhibition, apoptosis induction, and migration inhibition in vitro and tumor growth suppression in vivo. Conversely, knockdown of NKILA suppresses the effects of baicalein. Mechanistically, we found that NKILA inhibits IkBa phosphorylation, NF-kB nuclear translocation, and NF-kB activity. NKILA also enhances the inhibitory effects of baicalein on NF-kB signaling. Furthermore, the effects of NKILA on baicalein-induced NF-kB activity inhibition, cell growth inhibition, apoptosis induction, and migration inhibition are reversed by NF-kB nuclear translocation inhibitor JSH-23.