The inhibitory mechanism of luteolin on tumor necrosis factor (TNF)-${alpha}$-induced inflammation was investigated in HepG2 cells. Luteolin significantly suppressed TNF-${alpha}$-stimulated inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner without cytotoxicity. Phosphorylation and nuclear translocation of both transcription factors, nuclear factor (NF)-${kappa}B$ and activator protein (AP)-1, were also inhibited by luteolin treatment. Additionally, luteolin suppressed TNF-${alpha}$-induced c-Jun N-terminal kinase (JNK) phosphorylation, which is crucially related to regulating inflammation. SP600125, a JNK selective inhibitor, abolished the TNF-${alpha}$ triggered inflammatory signaling cascade. These results suggest that luteolin attenuates inflammatory responses by blocking NF-${kappa}B$ and AP-1 activation through suppressed JNK phosphorylation in TNF-${alpha}$-stimulated HepG2 cells.