The detection of circulating tumor DNA is important in cancer research and clinical practice.In the present study,we aimed to improve the sensitivity of downstream mutation detection of next-generation sequencing using the clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)system to selectively target wild-type fragments but with low or no cleavage activity to mutant fragments,followed by amplification using polymerase chain reaction.We selected different mutant sites of epidermal growth factor receptor gene(EGFR)-exon19 deletions in patients with lung cancer and constructed mixed templates of mutant and wild-type DNA comprising ratios of 10％to 0.01％to test the effectiveness of the enrichment method.The results showed that after CRISPR/Cas9 enrichment,a low concentration of mutant DNA fragments(0.01％)could be detected by Sanger sequencing,which represented a 1000-fold increase com-pared with the untreated samples.We further verified the feasibility of the introduced method and obtained similar results in clinical samples from patients with non-small cell lung cancer,indicating that this method has the potential to detect low copy number mutations at the early stage.