The mutation is the second most common genetic variant in Chinese non-small cell lung cancer (NSCLC) patients. At the 2019th World Conference of Lung Cancer, the -specific inhibitor AMG510 showed promising results in the phase I clinical trial. However, the frequency, clinical characteristics, and prognostic significance of the mutation in Chinese NSCLC patients are rarely reported. Next-generation sequencing was used to confirm the mutation status in 40,804 NSCLC patients from multiple centers (mCohort). Survival data were collected retrospectively from 1456 patients at one of the centers, the Guangdong Lung Cancer Institute (iCohort). In the mCohort, 3998 patients (9.8%) were confirmed to harbor a mutation, of whom 1179 (29.5%) had the subtype. In the iCohort, 130 NSCLC patients (8.9%) had a mutation and 42 (32.3%) had the subtype. The subgroup included more male patients (85.2% vs 67.4%,  < 0.0001) and more smokers (76.2% vs 53.4%,  = 0.02) than did the non- subgroup. Both the mutation group and mutation subgroup were associated with a shorter median overall survival (OS) than wildtype tumors (15.1 vs 26.7 months, hazard ratio HR  = 1.50,  = 0.002; 18.3 vs 26.7 months, HR  = 1.66,  = 0.007). In Cox regression analysis, smoking (HR = 1.39,  = 0.05) and stage IV disease (HR = 2.72,  < 0.001) remained as independent predictors of shorter OS. Both the mutation (HR = 1.30,  = 0.07) and mutation (HR = 1.47,  = 0.07) reached borderline significance. In the largest sample used thus for, our study found that approximately 10% of Chinese NSCLC patients had mutations. Of these, nearly 30% harbored the mutation subtype, which was most common in male smokers. The mutation is a biomarker of poor prognosis in Chinese NSCLC patients, which could potentially be improved by -specific inhibitors in the future.(296 words).