Background: In this study, we tried to investigate whether carbenoxolone, prunetin, and silibinin affect tumor necrosis factor (TNF)-α- induced MUC5AC mucin production and gene expression from human airway epithelial cells. Methods: Confluent NCI-H292 cells were pretreated with each agent (carbenoxolone, prunetin, and silibinin) for 30 min and then stimulated with TNF-α for 24 hours. The MUC5AC mucin gene expression and mucin protein production were measured by reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay, respectively. Results: Carbenoxolone, prunetin and silibinin inhibited the production of MUC5AC mucin protein induced by TNF-α; the 3 compounds also inhibited the expression of MUC5AC mucin gene induced by TNF-α. Conclusion: This result suggests that carbenoxolone, prunetin and silibinin can inhibit mucin gene expression and production of mucin protein induced by TNF-α, by directly acting on airway epithelial cells.