Background: We investigated whether prunetin significantly affects tumor necrosis factor-${alpha}$ (TNF-${alpha}$)-induced MUC5AC mucin gene expression, production, inhibitory kappa B ($I{kappa}B$) degradation and nuclear factor kappa B (NF-kB) p65 translocation in human airway epithelial cells. Methods: Confluent NCI-H292 cells were pretreated with prunetin for 30 minutes and then stimulated with TNF-${alpha}$ for 24 hours or the indicated periods. MUC5AC mucin gene expression and mucin protein production were measured by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The effect of prunetin on TNF-${alpha}$-induced degradation of $I{kappa}B$ and translocation of NF-${kappa}B$ p65 was investigated by western blot analysis. Results: We found that incubation of NCI-H292 cells with prunetin significantly inhibited mucin production and down-regulated the MUC5AC gene expression induced by TNF-${alpha}$. Prunetin inhibited TNF-${alpha}$-induced degradation of $I{kappa}B$ and translocation of NF-${kappa}B$ p65. Conclusion: This result suggests that prunetin inhibits the NF-${kappa}B$ signaling pathway, which may explain its role in the inhibition of MUC5AC mucin gene expression and production regulated by the NF-${kappa}B$ signaling pathway.