Naringenin, a natural predominant flavanone derived from plant food, has antifibrotic activity. The purposes of this study were to determine the effect of naringenin on myofibroblast differentiation and extracellular matrix (ECM) production in nasal polyp-derived fibroblasts (NPDFs) and to determine the molecular mechanism of the effect of naringenin on NPDFs. NPDFs were incubated and treated with transforming growth factor (TGF)-β1. The expression of alpha smooth muscle actin (α-SMA), fibronectin, and collagen type I mRNA was determined by a reverse transcription-polymerase chain reaction, and the expression of those proteins was determined by immunofluorescence staining or Western blotting. Expression of several signaling molecules of the TGF-β1 pathway was evaluated by Western blot analysis. Naringenin inhibits expression of an indicator of myofibroblast differentiation (α-SMA) and ECM production, including collagen type 1 and fibronectin. Naringenin only suppressed the expression of extracellular signal-regulated protein kinase (pERK)1/2 among evaluated signaling molecules. PD98059 (a specific inhibitor of ERK1/2 kinase) also suppressed the increased expression of fibronectin, collagen type I, and α-SMA in TGF-β1-induced NPDFs. These results suggest the possibility that naringenin may play an inhibitory role in the production of the ECM in the development of nasal polyps. Copyright © 2012 John Wiley & Sons, Ltd.