Abstract: Objective: To study the expression and clinical significance of p14^ARF and p16^INK4a proteins and to explore the correlationship between negative expressions of p14^ARF and p16^INK4a proteins in non-small cell lung cancer (NSCLC). Methods: The expressions of p14^ARF and p16^INK4a proteins were detected in 103 NSCLC samples by immunohistochemistry (S-P method). Results: The negative expression of p14^ARF was detected in 73 (70.87%) of the 103 NSCLC cases. The other 30 cases showed positive immunohistochemical result. While the negative expression of p16^INK4a was detected in 45 (43.69%) of 103 NSCLC cases. The other 58 cases showed positive immunohistochemical result. There was a significant difference between the negative rate of p14^ARF expression and of p16^INK4a expressions (P<0.01). In 103 NSCLC, 35 cases (33.98%) showed simultaneous loss in both proteins. The negative rates of p14^ARF and p16^INK4a co-expressions in squamous cell carcinoma, adenocarcinoma and bronchioloalveolar carcinoma were 55.88% (19/34), 27.27% (9/33) and 19.44% (7/36), respectively, and the squamous cell carcinoma group was significantly higher compared to the others (P<0.01). Rank correlation analysis revealed that there was no correlation between negative expression of p14^ARF and of p16^INK4a proteins in NSCLC(P>0.05). Of the 65 samples analyzed from NSCLC patients, the negative rate of p14^ARF and p16^INK4a expressions were 54.05%(20/37) and 35.14%(13/37) in the groups of clinical stageⅠ+Ⅱ respectively, the negative rate of p14^ARF and p16^INK4a expressions were 78.57%(22/28) and 60.71%(17/28) in the groups of clinical stage Ⅲ+Ⅳ respectively. Either p14^ARF or p16^INK4a negative expression was closely related to clinical stage (P<0.05). Conclusion: Expression alteration of INK4a-ARF gene has the tendency of histopathological specificity. Moreover, there is no correlation between negative expression of p14^ARF and p16^INK4a proteins in NSCLC.