Objective To investigate the diagnostic efficacy of circulating tumor cells (CTC) combined with CT in the nature of pulmonary nodule lesions. Methods From March 2019 to August 2021, 82 patients with suspected pulmonary nodule lesions in Bao′an Central Hospital Affiliated to Guangdong Medical College were selected as the subjects. After admission, they underwent chest CT imaging examination and CTC examination. The pathoiogical tissue examination was used the "gold standard" to analyze the diagnostic efficacy of CTC and combined CT, and to determine the nature of small pulmonary nodules. Results Among 82 patients with suspected pulmonary nodule lesions, 61 patients were diagnosed with pulmonary nodule lesions by histopathological examination, and the diagnosis rate was 74.39%. Among them, there were 16 cases (26.23%) of benign nodules and 45 cases (72.77%) of malignant nodules. 57 cases of small pulmonary nodules were diagnosed by CTC combined with CT examination, there were 20 benign nodules and 37 malignant nodules, and the accuracy was 85.37%, the diagnostic sensitivity was 86.89% (53/61), the specificity was 80.95% (17/21), the positive predictive value was 92.98% (53/57), the negative predictive value was 68.00% (17/25),and the AUC was 0.894. Conclusion CTC examination has a higher detection rate in small pulmonary nodule lesions,and the examination accuracy is higher than that of CT imaging results, and the combined examination of the two can improve the diagnostic efficiency and provide a reference for clinical diagnosis and treatment.