Abstract: Objective:To detect the expression of Smad4 mRNA in non-small cell lung cancer (NSCLC), to analyze the expression and the relationship between Smad 4 mRNA and different clinicopathologic characteristics, and to investigate the development and metastasis of Smad4 mRNA in non-small cell lung cancer. Methods:The study included 40 cases of NSCLC as the experimental group and 18 cases of normal lung tissues as the control, which used real-time quantitative polymerase chain reaction ( PCR ) to detect the expression of Smad4 mRNA. The average age of experimental group was (55 .3 ± 7.1 ) years ( range, 41 -68 years ). The experimental group included 22 males and 18 females, 27 cases of squamous cell carcinoma, 13 cases of adenocarcinoma,24 cases of non-lymph node metastasis, and 16 lymph node metastasis cases. Results:The level of Smad4 mRNA expression ( 2.2425 ± 0.6057 ) in the non-small cell lung cancer was lower than that of the adjacent lung tissue ( 4.4850 ± 1.0648 ) ( P < 0.001 ) and the difference was statistically significant. The differences in Smad4 mRNA expression in terms of differences in age, gender, and pathological type were not statistically significant. The expression in poorly differentiated carcinoma was ( 1.9648 ± 0.5170 ), the expression in the well-differentiated cells was ( 2.5495 ± 0.5545 ) ( P = 0.0014 ), and the difference was statistically significant. The expression was ( 1.8656 ± 0.4859 ) in the cases with lymph node metastasis and ( 2.4938 ± 0.5502 ) ( P = 0.0007 ) in the cases with no lymph node metastasis; the difference was statistically significant. The expression in the cases with no pleural invasion was ( 2.4668 ± 0.5657 ), whereas it was ( 1.9683 ± 05483 ) ( P = 0.0078 ) among cases with pleural invasion. The TNMⅠand Ⅱstages were (2.5281 ± 0.4516 ), whereas the TNM Ⅲand Ⅳstages were (1.9268 ± 0.6058 ) ( P = 0.0010 ); the difference was statistically significant. The patients were followed up for10-76months, and 25of the 40patients with non-small cell lung cancer survived more than 3 years, accounting for 62.50%. Upon examination, the Smad4 mRNA expression in NSCLC was related to patientprognosis ( χ2= 16.9620, P < 0.0001). Conclusion:Low Smad4 mRNA expression may play an important role in the development of non-small cell lung cancer. Testing Smad4 mRNA may have a certain value in predicting the prognosis of non-small cell lung cancer.