Abstract: Objective: To investigate the expression of Coxsackie and Adenovirurus Receptor (CAR) and its relationship with the origin and progression of lung cancer (squamous cell carcinoma and adenocarcinoma) and to approach the theoretical foundation for designing the adenovirus vector which could be used in the gene therapy for lung cancer. Methods: The expression of CAR in 112 cases of lung cancer(65 cases of squamous cell carcinoma and 47 cases of adenocarcinoma) was detected by immunohistochemistry. The difference of CAR expression in squamous cell carcinoma, adenocarcinoma and para-cancer normal lung tissues was analyzed by statistical software (SPSS 10.0). Results: The expression of CAR in normal lung tissues was lower than that in tumor-adjacent tissues. The expression of CAR was 34.75% higher in squamous cell carcinoma than that in tumor-adjacent tissues and the difference was significant (P<0.01). The expression of CAR was 38.30% higher in adenocarcinoma than that in tumor-adjacent tissues. The positive rate of CAR expression was 43.08% in squamous cell carcinoma, and 70.21% in adenocarcinoma, with a significant difference(P<0.01). But no significant difference was found(P>0.05) among different stages of squamous cell carcinoma(stage Ⅰ~Ⅲ). Furthermore, we found that CAR was expressed at a high level in bronchioalveolar carcinoma which is a subtype of the lung adenocarcinoma. Conclusion: The increased expression of CAR in lung cancer suggests that it is related to the occurrence and development of lung cancer especially to adenocarcinoma. Our research provided the theoretical foundation for the gene therapy with adenovirus vector for lung cancer.