Objective To study the tumor markers carcinoembryonic antigen (CEA) and squamous cell carcinoma associated antigen (SCCAg), neuron specific enolase (NSE) in advanced non-small cell lung cancer, in the process of evaluation of the efficacy of clinical application. Methods 78 cases of advanced non-small cell lung cancer patients as the research object, according to the targeted therapy after curative effect is divided into partial remission group 39 cases, 24 cases of stable disease group, 15 cases in group, compared three groups of subjects targeted drug therapy before and after eight weeks of treatment, tumor markers CEA, SCCAg and NSE in serum the level changes of tumor markers in evaluating the therapeutic effect of clinical application. Results The results of different pathological types of non-small cell lung cancer tumor markers: CEA increased statistically in any group of squamous cell carcinoma, squamous adenocarcinoma and adenocarcinoma; SCCAg increased and there was significant difference in any group in adenocarcinoma, squamous adenocarcinoma, squamous cell carcinoma; NSE is the highest in adenocarcinoma, no statistically significant difference in squamous cell carcinoma, squamous adenocarcinoma; partial remission group of patients with non-small cell lung cancer tumor markers CEA, SCCAg, NSE serum levels were decreased, the difference was statistically significant; stable disease group non-small cell cancer tumor markers CEA, SCCAg and NSE serum levels no significant change; partial remission in patients with tumor progression of non-small cell carcinoma markers CEA, SCCAg, NSE serum levels were elevated, the difference was statistically significant. Conclusion The monitoring of tumor markers is a reliable approach to understand the effectiveness of molecular targeted therapies, and is also the basis for molecular targeted drug selection.