Objective To explore the relationship of CD40 expression in non-small cell lung cancer (NSCLC) and its clinical significance. Methods Immuno-histochemical staining (IHS) and enzyme-linked immunosorbent assay (ELISA) were performed to detect expression of CD40 in 60 NSCLC tissues, 15 paratumor tissues and their peripheral blood. Results ( 1) CD40 positive tumor cells could be detected in NSCLC tissues(P <0.05). (2) Expression rate of CD40 positive tumor cells in tumor tissues with lymph node metastases was higher than those without lymph node metastases (P <0. 05). CD40 expression in tumor tissues in stage Ⅲ ~ Ⅳ was higher than those in stage Ⅰ~ Ⅱ. ( P < 0. 05). (3) Level of soluble CD40(sCD40) of NSCLC group was higher than the health control group. Further analysis demonstrated levels of sCD40 in serum was positively correlated with expression of CD40 in NSCLC tissues. Conclusion There is relationship between CD40 expression in NSCLC and clinical stage and metastases. CD40 may participate in tumor progression of disease and play an important role of tumor immune escape through enhancing the ability of invasion.