Background and Objective: Compared with tissue biopsy, liquid biopsy is the most preferable non-invasive promising method in personalized medicine, although it has many limitations in isolating circulating tumor cells (CTC). Lung cancer associated mortality is drastically increased due to a shortfall of early-stage detection, which remains a challenge. Herein, we aimed to detect lung cancer at an early-stage using CellCollector device. Methods: 39,627 volunteers underwent low-dose computed tomography; 2508 cases with pulmonary nodules and 7080 with no pulmonary nodules were chosen. After follow-up, 24 patients were diagnosed with early-stage non-small cell lung cancer (NSCLC), and subjected to CTC detection using CellCollector, along with 72 healthy volunteers. Immunofluorescence staining for EpCAM/CKs and CD45 were performed for CTC validation. Results: Fifteen out of twenty-four (stage I, n = 18; stage II, n = 6) early-stage lung cancer patients were found to be CTC-positive, whereas no CTC was found in the control group. Genetic mutation of TP53, ERBB2, PDGFRA, CFS1R and FGFR1 in the CTC revealed 71.6% of the mutation sites similar to the tumor tissues of 13 patients. Molecular characterization revealed higher expression of protein PD-LI in CTC (40%) as compared to tumor tissue (26.7%). Moreover, CTC clusters were detected in 40% of patients. Conclusion: CTC detection using the CellCollector in early-stage NSCLC had a relative high capture rate. Moreover, CTC analysis is a prospective setting for molecular diagnostic in cases when tumor tissue biopsy is not desirable.