Abstract: Objective To evaluate the diagnostic value and safety of percutaneous lung biopsy under CT guidance for sub-solid nodules lesions. Methods The clinical data and follow-up data of 26 cases of pulmonary sub-solid nodules lesions that performing percutaneous lung biopsy under CT guidance in our hospital were analyzed retrospectively. The ratio of correct diagnosis of sub-solid nodules, diagnostic sensitivity diagnostic specificity of malignant sub-solid nodules and the incidence of complications were calculated. Results Each tissue was successfully obtained from 26 cases of pulmonary solid nodules by once puncture. The success rate of puncture was 100%. Twelve cases (12/26, 46.15%) of malignant tumors were diagnosed. Eight cases were adenocarcinoma, 1 case was adenosquamous carcinoma, 2 cases were squamous cell carcinoma, 1 case was poorly differentiated carcinoma, 1 case adenocarcinoma accompanied with fungal infection. Fourteen cases were benign lesions (14/26, 53.85%), 1 case of them was infiltrated with small amount of inflammatory cells and interstitial hyperplasia that diagnosed as adenocarcinoma by endobronchial ultrasonography later; 1 case was aspergillosis and 8 cases were inflammation (2 cases of patients with chronic inflammatory had progressed after the anti-inflammatory treatment and they were diagnosed as adenocarcinoma in other hospital after resection. The remaining 6 patients with chronic inflammation were all healed after anti-infective treatment); 1 case with mild interstitial vasculature dilatation and congestion was confirmed as inflammation after anti-infective treatment. One case diagnosed as a few well-differentiated squamous epitheliums, which was absorbed after anti-infection treatment. Two cases of tuberculosis were diagnosed. Small pneumothorax was found in 2 patients (7.69%). Small amount of hemoptysis occurred in 5 patients (19.29%). The ratio of correct diagnosis of sub-solid nodules performed by CT-guided percutaneous pulmonary puncture was 84.62%(22/26). The sensitivity and specificity of the diagnosis of malignant sub-solid nodules were 80% (12/15) and 100%, the incidence of complications was 26.92%, the incidence of severe complications was 0%. Conclusion CT-guided percutaneous puncture biopsy can safely and effectively diagnose pulmonary ground glass opacity lesions.