Abstract: Objective To examine p16 gene expression in human non-small cell lung cancer (NSCLC) and to took for correlations among P16 expression and clinicopathologic features and prognosis. Methods With S-P immunohistochemistry method,investigated p16 protein expression in 80 patients with primary NSCLC and 40 with lung benign diseases (as control) with archival paraffin specimens. Results The positive rate of p16 expression in NSCLC and lung benign diseases were 55% (40/80) and 92.5% (37/40),respectively.There was significant difference between the two groups.(P<0.005).The positive rate of p16 expression was related to clinical stage of NSCLC.lower p16 expression in NSCLC was seen with advanced pathological stage of disease.The positive rate of p16 expression in NSCLC had no correlation to its histopathological subtype. Conclusion Immunohistochemical analysis of the p16 gene/MTS1 products is feasible.These results suggest that p16 /MTS1 down-regulation expression plays an important role in tumorigenesis or tumor progression of NSCLC.Aberrant expression of p16/MTS1 gene may assess the prognosis in NSCLC.