Purpose　Approximately　30%　of　NSCLC　patients　cannot　obtain　tissue　sample　or　sufficient　tissue　sample　for　molecular　subtyping.　Cell-free　circulating　tumor　DNA　(ctDNA)　in　plasma　is　a　potential　alternative　specimen　type　to　assess　genomic　variants　in　patients　with　non-small　cell　lung　cancer　(NSCLC).　The　purpose　of　this　study　was　to　identify　the　genomic　alteration　profile　of　ctDNA　in　real-world　Chinese　NSCLC　patients.　Methods　A　total　of　325　subjects　with　pathological　diagnosis　of　NSCLC　were　enrolled.　10　ml　Peripheral　blood　was　collected　in　streck　tube,　and　ctDNA　NGS　analysis　was　carried　out　using　an　Ampliseq-based　11-gene　panel.　Results　295　out　of　325　patients　(90.8%)　had　detected　ctDNA　results.　In　62.1%　(183/295)　of　these　cases,　at　least　one　genomic　alterations　was　detected.　Frequency　altered　genes　were　EGFR　(27.8%),　TP53　(22.7%),　KRAS　(21.36%),　and　PIK3CA　(4.75%).　EGFR　mutation　was　associated　with　female,　younger　age　(＜　65　years),　and　adenocarcinoma.　The　most　common　mutations　in　EGFR　were　L858R　(39.4%),　exon19　deletions　(31.73%),　and　T790M　(18.3%);　G13S　was　the　most　common　alterations　in　KRAS.　TP53　mutation　was　most　occurred　in　exon7　and　exon8.　TP53　mutation　was　significantly　more　common　in　patients　with　history　of　radiochemotherapy/chemotherapy　therapy,　and　T790M　was　mainly　found　in　patients　with　TKIs　treatments.　Co-existence　EGFR　mutation　with　KRAS　and　different　multiple　gene　co-mutation　panels　were　detected.　Conclusion　In　Chinese　NSCLC　patients,　EGFR　mutation　was　significantly　associated　with　female,　younger　age　(＜　65　years),　and　adenocarcinoma.　Genomic　profiles　of　NSCLC　were　associated　with　the　treatment　history;　TP53　mutation　was　significantly　more　frequent　in　the　patients　with　history　of　radiochemotherapy/chemotherapy　therapy.　Various　multiple　genes　co-mutation　panels,　especially　EGFR　and　KRAS　co-mutation,　were　observed　in　the　ctDNA　of　Chinese　NSCLC　patients.