Background: Molecular profiling is limited by tumor heterogeneity and access to sufficient tissue for comprehensive analysis. ctDNA is promising as a minimally-invasive liquid biopsy for testing gene alterations and monitoring personalised treatment strategies. Because of its high expense, translation of the sensitive and accurate next generation sequencing (NGS) into routine cancer care has been slow. Methods: We retrospectively reviewed 60 advanced NSCLC pts who were performed gene test prior to treatment using tissue by ARMS. Blood collections were performed after disease progression and analysed by NGS using a 10-gene panel (EGFR, KRAS, BRAF, HER2, PIK3CA, ALK, ROS1, RET, MET and TP53). We evaluated the significance of the outcome of panel testing by NGS in guiding the subsequent treatment in clinical practice. Results: ctDNA profiling detected alterations in 50 pts (83%). TP53 (53%), EGFR (48%) and KRAS (15%) were the most common abnormalities detected. Additionally, MET (8%), ALK (3%), HER2 (3%) and PIK3CA (2%) mutations were detected, respectively. Sensitizing mutations were detected in 22 pts (37%) prior to treatment using tissue by the method of ARMS, including 20 EGFR mutations and 2 ALK fusions, and all pts received tyrosine kinase inhibitor (TKI) as first-line therapy. Among 20 EGFR mutant pts, T790M mutation was detected in 9 pts (45%), KRAS mutation was detected in 4 pts (20%), and TP53 mutation was detected in 12 pts (60%), while MET amplification was found in 1 pt (5%). 1 KRAS mutation and 1 TP53 mutation were detected in 2 ALK –TKI resistant pts, respectively. 28 pts (47%) reported as tissue negative had a positive liquid biopsy, including 4 MET 14 exon skipping mutations, 2 EGFR 19 DEL, 4 EGFR L858R and 1 EGFR L861Q, and 2 EGFR T790M mutations. The mutation abundance is all below 1%, except 2 EGFR 19 DEL and 4 L858R. Ten pts received TKIs; 2 got parcial responses, 5 stable diseases and 3 progressive disease. Conclusions: ctDNA can be used as a ‘liquid biopsy’ for NSCLC pts, and NGS, as a highly sensitive method to detect mutations with low mutation abundance, can provide more chances to pts to receive precise treatment.