PURPOSE: Accumulating evidences have been identified that CSCs play a pivotal role in tumor regeneration, metastasis and drug resistance in lung cancer. Toll-like receptor 9 (TLR9), when activated by its ligands CpG oligodinucleotides (CpG-ODN), can trigger IKK/NF-kB, MAPK/AP-1 and PI3K/Akt signal pathways, and finally contribute to the growth and metastasis of lung cancer cells. Most recently, Andreas and colleagues identified that TLR9 is a critical functional marker for glioma stem cells and a target for the delivery of efficacious glioma treatment. While the role of TLR9 in other stem cells, including lung cancer stem cells, haven’t been elucidated until now. Thus this study aims to investigate the role of TLR9 in lung CSC.