Objective: The present study, CLUS version 2.0, was conducted to evaluate the performance of new techniques in improving the implementation of lung cancer screening and to validate the efficacy of LDCT in reducing lung cancer-specific mortality in a high-risk Chinese population.Methods: From July 2018 to February 2019, high-risk participants from six screening centers in Shanghai were enrolled in our study. Artificial intelligence, circulating molecular biomarkers and autofluorescence broncho-scopy were applied during screening. Results: A total of 5087 eligible high-risk participants were enrolled in the study; 4490 individuals were invited, and 4395 participants (97.9%) finally underwent LDCT detection. Positive screening results were observed in 857 (19.5%) participants. Solid nodules represented 53.6% of all positive results, while multiple nodules were the most common location type (26.8%). Up to December 2020, 77 participants received lung resection or bi-opsy, including 70 lung cancers, 2 mediastinal tumors, 1 tracheobronchial tumor, 1 malignant pleural meso-thelioma and 3 benign nodules. Lung cancer patients accounted for 1.6% of all the screened participants, and 91.4% were in the early stage (stage 0-1).Conclusions: LDCT screening can detect a high proportion of early-stage lung cancer patients in a Chinese high -risk population. The utilization of new techniques would be conducive to improving the implementation of LDCT screening.