ABSTRACT: This meta-analysis was to explore the clinical significance of circulating tumor cells (CTCs) in predicting the tumor response to chemotherapy and prognosis of patients with lung cancer.We searched PubMed, Embase, Cochrane Database, Web of Science and reference lists of relevant articles. Our meta-analysis was performed by Stata software, version 12.0, with a random effects model. Risk ratio (RR), hazard ratio (HR) and 95% confidence intervals (CI) were used as effect measures.8 studies, including 453 patients, were eligible for analyses. We showed that the disease control rate (DCR) in CTCs-negative patients was significantly higher than CTCs-positive patients at baseline (RR = 2.56, 95%CI [1.36, 4.82], p < 0.05) and during chemotherapy (RR = 9.08, CI [3.44, 23.98], p < 0.001). Patients who converted form CTC-negative to positive or persistently positive during chemotherapy had a worse disease progression than those with CTC-positive to negative or persistently negative (RR = 8.52, CI [1.66, 43.83], p < 0.05). Detection of CTCs at baseline and during chemotherapy also indicated poor overall survival (OS) (baseline: HR = 3.43, CI [2.21, 5.33], p<0.001; during chemotherapy: HR = 3.16, CI [2.23, 4.48], p < 0.001) and progression-free survival (PFS) (baseline: HR = 3.16, 95%CI [2.23, 4.48], p < 0.001; during chemotherapy: HR = 3.78, CI [2.33, 6.13], p < 0.001).Detection of CTCs in peripheral blood indicates poor tumor response to chemotherapy and poor prognosis in patients with lung cancer.