Abstract: Objective: To obtain data results from the cancer genome altas (TCGA) database and analyze the correlation between clinical features and prognosis of patients with non-small cell lung cancer (NSCLC) and the types of hotspot driver mutations. Methods: The clinical data of 115 hospitalized patients with NSCLC (NSCLC group) were retrospectively analyzed.Gene mutation was detected by second-generation high-throughput sequencing,and the clinical data and gene mutation data of NSCLC were obtained by combining TCGA database to analyze the relationship between gene mutation and patient prognosis. Results: High-throughput sequencing results showed that the total gene mutation rate of NSCLC patients was 76.52% (88/115),and the human epidermal growth factor receptor (EGFR) mutation rate was 53.91% (62/115).The total mutation rate of genes in TCGA database was 93.57%,and the mutation rate of EGFR gene was only 7%.There was significant difference between NSCLC patients with EGFR unit point mutation and co-mutation in whether distant metastasis occurred (P<0.05).The results of multi-factor analysis showed that the number of gene mutations was an independent risk factor affecting the prognosis of patients (P<0.05). Conclusions: EGFR point mutation and co-mutation have a certain effect on the prognosis of NSCLC patients,and patients with polygenic co-mutation have a better prognosis,and clinical treatment should pay attention to the situation of gene co-mutation.