e21023 Background: CT-guided percutaneous lung biopsy is important for the diagnosis of lung cancer especially in the area of precision medicine. In ASCO 2015, we reported that "Liquid withdraw" technique (to inject small amount of liquid while withdraw of the needle) can prominently reduce incidence of pneumothorax when combined with co-axial technigue in 38 cases. In ASCO 2017, we retrospectively studied 90 patients undergoing CT-guided percutaneous lung biopsy to investigate the role of this technigue in reducing complications and promoting biopsy effectiveness. Based on the above studies, we conducted a prospective study to further evaluate the role of this technique in conjunction with the other eight techniques (Position compensation, Cushion for position adjustment, Skin expansion in advance, Secondary location outside the pleura, Needle core instantaneous replacement, Mutual fix, Simultaneous bleeding arrest, and Cortical displacement) in the precision diagnosis and treatment of lung cancer. Methods: From January 16th, 2018 to October 11th, 2021, a total of 150 CT-guided percutaneous transthoracic biopsy procedures performed in 146 patients were prospectively evaluated. The pathologies and complications secondary to biopsy procedure were analyzed. Pneumothorax and bleeding was graded as mild/very mild, moderate, and severe. All patients were divided into two groups: the lesion depth was < 30mm from the pleura and ≥30mm from pleura. Different complications between the two groups were analyzed using Pearson’s Chi-squared test for categorical values. Results: 148 cases was diagnosed out of 150 biopsies (98.67%), of which 118 cases were malignant (108 cases can be identified which type and source (91.53%), in which 68 cases were adenocarcinoma), 30 cases were benign. Pneumothorax occurred in 27 (18%) cases, among which, 12% were very mild pneumothorax and 6% were mild to moderate pneumothorax. 44 cases (29.33%) happened bleeding, among which, 21.33% could be classified as very mild, while 8% could be classified as mild to moderate. No infection, tumor implantation or aeroembolism observed. There were no statistically significant differences in the incidence of pneumothorax and bleeding at different distances from the pleura( < 30mm vs ≥30mm, P>0.05). Conclusions: This series of new techniques in CT-guided percutaneous lung biopsy significantly reduced the incidence of pneumothorax and bleeding and were preliminarily proved that can facilitate acquiring more tumor tissue for molecular testing and re-biopsy of lung cancer. Clinical trial information: ChiCTR1800017958 .