Wnt/beta-catenin signaling plays an important role not only in cancer, but also in cancer stem cells In this study, we found that beta-catenin and OCT-4 was highly expressed in cisplatin (DDP) selected A549 cells Stimulating A549 cells with lithium chloride (LiCl) resulted in accumulation of beta-catenin and up-regulation of a typical Writ target gene cyclin D1 This stimulation also significantly enhanced proliferation, clone formation, migration and drug resistance abilities in A549 cells Moreover. the Up-regulation of OCT-4, a stem cell marker, was observed through real-time PCR and Western blotting In a reverse approach, we inhibited Wilt signaling by knocking down the expression of beta-catenin using RNA interference technology This inhibition resulted in clown-regulation of the Wilt target gene cyclin D1 as well as the proliferation, clone formation, migration and drug resistance abilities Meanwhile, the expression of OCT-4 was reduced after the inhibition of Wnt/beta-catenin signaling Taken together. Our Study provides strong evidence that canonical Wnt signaling plays an important role in lung cancer stem cell properties, and it also regulates OCT-4, a lung cancer stem cell marker (C) 2010 Elsevier Inc All rights reserved