Abstract: Objective To analyze the diagnostic value and safety of transbronchial lung cryobiopsy （TBLC） in interstitial lung disease （ILD） and malignant lung lesions. Methods This study is a non-randomized controlled trial. Using the method of non-random sampling, 55 patients with ILD and pulmonary space-occupying lesions who were hospitalized in the Department of Respiratory and Critical Care Medicine of Beijing Tsinghua Changgung Hospital affiliated with Tsinghua University from January 2015 to February 2022 were selected. All patients were divided into the ILD group （n = 31） and pulmonary space-occupying lesion group （n = 24）. Basic information and clinical data were collected in both groups. Transbronchial forceps biopsy （TBFB） and TBLC techniques were sequentially employed to obtain lung biopsy samples based on intraoperative conditions, with no pre-inserted balloon in the TBLC group. Biopsy samples in both groups were sent for pathological examination. Kappa test was used to compare the consistency of pathological diagnosis between TBFB and TBLC. The receiver operating characteristic （ROC） curve and Logistic regression analysis were used to analyze the diagnostic efficiency of TBLC and TBFB alone or these two combined for malignant pulmonary lesions. Results Among the 55 patients, 61.8% （34/55） were male and 40.0% （22/55） were smokers. 40 cases （72.7%） had mild bleeding, 14 cases （25.5%） had moderate bleeding, and 1 case （1.8%） had no bleeding. No severe bleeding events or pneumothorax events occurred. In the ILD group, 19 patients were male and 12 female, aged （58.65±14.47） years on average, ranged from 16 to 76 years. The diagnoses of 17 patients were confirmed and 14 unconfirmed cases in this group. Among the confirmed cases, idiopathic pulmonary interstitial fibrosis （n = 4） and organizing pneumonia （n = 4） accounted for the highest percentage. In the pulmonary space-occupying lesion group, 15 patients were male and 9 female, aged （63.17±10.77） years old on average, ranged from 40 to 79 years. The diagnoses of 21 patients were finally confirmed and 3 unconfirmed cases in this group. Among the confirmed cases, there were 16 cases of malignant lung lesions, primarily lung adenocarcinoma （n = 7）. In the ILD group, the diagnostic rate of TBFB was 19.4% and 51.6% for TBLC, and the diagnostic rate in the TBLC group was higher than that in the TBFB group （P = 0.008）. In the pulmonary space-occupying lesion group, the diagnostic rate of TBLC was also superior to that of TBFB （79.2% vs. 37.5%, P = 0.002）. The area under the ROC curve of TBFB and TBLC in the diagnosis of malignant lung lesions was 0.77 （95%CI： 0.57-0.98） and 0.83 （95%CI： 0.66-1.00）, respectively. Conclusion TBLC has significant advantages in the diagnosis of ILD and lung malignancies, with a low risk of bleeding and high safety in clinical practice.