Genotype-directed therapy is critical to the treatment strategy for advanced non-small cell lung carcinoma. Compared with the traditional biopsy sample, ctDNA is easier to sample and monitor in real time. Therefore, we extracted ctDNA from peripheral blood samples of 86 patients with advanced NSCLC for detection. We carried out ultra-highdepth targeted capture sequencing on seven genes. We found that 47.67% (41/86) of patients had at least one potentially manipulable variant. Of the 100 identified variants, 83 were potentially actionable variants. These single nucleotide variations, insertions, and deletions were most common in EGFR (46%), next were KRAS (26%), MET (20%), PIK3CA (15%), MAP2K1 (9%), BRAF (4%), NRAS (2%). Twelve new pathogenic mutants were identified by 12 protein function prediction algorithms. These results help us to better understand the mutation of NSCLC.