Background: Lung cancer is one of the leading causes of all cancerrelated deaths worldwide and majority is diagnosed as non-small cell lung cancer (NSCLC).Although remarkable advances in treatments have been made, the prognosis of NSCLC is still poor.CD137 ligand, a member of the tumor necrosis factor (TNF) family, is expressed not only on antigen presenting cells (APC), but also on various tumor cells, and crosslinking of CD137L leads to production of IL-8 by tumor cells.The objective of the current study was to investigate the expression of CD137L on NSCLC tissues and the effects of CD137L signaling in NSCLC progression.Methods: Expression of CD137L was assessed by immunohistochemistry of 102 NSCLC tissues and five normal adjacent lung tissues.The correlation of CD137L expression with clinical characteristics and prognosis were determined by statistical analysis.The protein level of CD137L in NSCLC cell lines, cell apoptosis and cell cycle assay were performed by FACS analysis.Cell proliferation was determined by CCK-8 assay.Western blotting was used to identify the apoptosis signaling mechanisms induced by ligation of CD137L.Results: CD137L expression was found in 57 of 102 (55.9%) NSCLC samples and correlated with TNM stage (P =0.005), tumor differentiation (P =0.002), and better prognosis(P <0.001).Moreover, CD137L signaling in H1650 cells which expressed high level of CD137L inhibited proliferation, induced apoptosis and cell cycle rest.In addition, the cell apoptosis induced by CD137L signals occurs via the activation of intrinsic pathway and depended on phosphorylation of JNK.Conclusions: Expression of CD137L was associated with better prognosis, and CD137L ligation on NSCLC cells resulted in inhibition of proliferation and induction of cell death.This result indicates that CD137L could be developed as a potential therapeutic target of NSCLC.