Abstract: Objective To evaluate the clinical value of ligand-targeted PCR method in detecting tumor cell (TC) levels in the pleural effusion of patients with non-small cell lung cancer (NSCLC). Methods We enrolled 50 NSCLC patients who were initially diagnosed as NSCLC with pleural effusion from January to December 2013 in Anhui Provincial Hospital. The samples of pleural effusion from each patient were collected and tumor cell levels in the pleural effusion were detected by circulating cell detecting system. The correlations between the tumor cell level and clinical characteristics, pathological category, performance status (PS) score, carcino-embryonic antigen (CEA) level and metastasis status were analyzed. The diagnostic positive rate of CTC detection method was compared with that of routine cytological examination method. Results The TC level in pleural effusion was not correlated to gender, age or pathological types (P>0.05). The patients with 3 points in PS score had a higher TC levels in pleural effusion than those with 0, 1 and 2 points (P<0.01). TC level was positively correlated to CEA in pleural effusion (r=0.667, P<0.01) and the numbers of metastatic sites (P<0.01). TC level was also significantly higher in patients with positive cytological examination than that in negative group(261.74±272.44)/ml vs. (90.61±144.24)/ml, P<0.01. Notably, in some patients whose TC level was increased remarkably, routine cytological examination was negative. Conclusion Ligand-targeted PCR method might be more efficient than exfoliated cell examinations method in detecting tumor cell level in the pleural effusion of NSCLC patients, and helpful for differential diagnosis and prognosis assessment.