Arctigenin (ARC) is a lignan and is abundant in Asteraceae plant which possesses anti-inflammatory and anti-cancer activities. The current study was performed to investigate if ARC affects cancer progression and metastasis focusing on epithelial–mesenchymal transition (EMT) using invasive human lung cancer cell line, A549. No toxicity was observed in the cells treated with different doses of ARC (12-100 µM). The treatment of ARC repressed TGF-β-stimulated changes of metastatic morphology and cell invasion and migration. ARC inhibited TGF-β-induced phosphorylation and transcriptional activity of SMAD2/3 and expression of snail in dose-dependent and time-dependent manners. ARC also decreased expression of N-cadherin and increased expression of E-cadherin in dose-dependent and time-dependent manners. These changes were accompanied with decreased amount of nuclear phospho-SMAD2 and SMAD3, and nuclear translocation of SMAD2 and SMAD3. Moreover, ARC repressed TGF-β-induced phosphorylation of ERK. Our data demonstrate anti-metastatic activity of ARC in lung cancer model. Key words: ARC, TGF-β, EMT, Lung cancer