Non-small cell lung cancer (NSCLC) is a major public health problem worldwide and leads to a high mortality. NSCLC is always diagnosed in late stages because of its unapparent symptoms. However, cell-free DNA (cfDNA) may serve as a new potential biomarker to detect early stage of non‑small cell lung cancer. Here we recruited 10 non-small cell lung cancer patients to obtain fresh tumor tissue, peripheral blood lymphocytes (PBLs), and plasma. CfDNAs from 13 elderly people and 7 middle-age smokers were also extracted as controls. Illumina HiSeq X10 was used to perform next-generation sequencing to evaluate differences in mutations among different samples. The result indicated that tumor DNA and its matched plasma cfDNA samples showed high concordance in their mutation patterns. Mutation rate of cfDNA was generally lower than that of tumor tissue and higher than that of PBLs. The plasma cfDNA concentration of NSCLC patients (69.2±46.9 ng/ml) is significantly higher than that of elderly people (32.5±5.2 ng/ml, t=2.96, p=0.007) and middle-aged smokers (17.9±9.1 ng/ml, t=2.83, p=0.013). Five mutations (PTEN_c.1375A>G, TP53_c.94G>A, STK11_c.816C>T, PIK3CA_c.1633 G>A, PIK3CA_c.2038G>C) were only identified in NSCLC patients but not in healthy people. Our conclusion was that cfDNA has a similar mutation pattern with its matched tumor tissue DNA. A high concentration of cfDNA and tumor specific mutations in cfDNA may serve as potential non-invasive biomarkers to detect early-stage non‑small cell lung cancer.