To evaluate whether postoperative circulating tumor DNA (ctDNA) in plasma of patients with non-small cell lung cancer (NSCLC) can be used as a biomarker for early detection of molecular residual disease (MRD) and prediction of postoperative recurrence. This study subjects were evaluated patients with surgical resected non-small cell lung cancer. All eligible patients underwent radical surgery operation followed by adjuvant therapy. Tumor tissue samples collected during operation were used to detect tumor mutation genes, and blood samples collected from peripheral veins after operation were used to collect ctDNA. Molecular residue disease (MRD) positive was defined as at least 1 true shared mutation identified in both the tumor sample and a plasma sample from the same patient was. Positive postoperatively ctDNA was associated with lower recurrence-free survival (RFS).The presence of MRD was a strong predictor of disease recurrence. The relative contribution of ctDNA-based MRD to the prediction of RFS is higher than all other clinicopathological variables, even higher than traditional TNM staging. In addition, MRD-positive patients who received adjuvant therapy had improved RFS compared to those who did not, the RFS of MRD-negative patients receiving adjuvant therapy was lower than that of patients not receiving adjuvant therapy. Post-operative ctDNA analysis is an effective method for recurrence risk stratification of NSCLC, which is beneficial to the management of patients with NSCLC.