The treatment of non-small cell lung cancer (NSCLC) has evolved from a purely histological type-based approach to an individualized era based on molecular typing. To date, several clinical studies such as IPASS and NEJGSG2002 have confirmed that EGFR-TKI drugs represented by gefitinib have good efficacy in the first-line treatment of patients with EGFR mutations. Therefore, since the new NCCN guidelines for lung cancer in 2011, gefitinib has been recommended as the EGFR-TKI drug for the first-line treatment of patients with EGFR-mutated NSCLC, and there is no evidence of efficacy difference between several TKI drugs. Given that most of the current studies show no significant difference in overall survival between first-line use of TKI drugs and first-line use of chemotherapy drugs, a platinum-containing third-generation two-drug combination chemotherapy regimen is recommended for patients with ECOG-good NSCLC with unknown EGFR mutations. Guan Xiaoqian, Department of Oncology, The Third Affiliated Hospital of Southern Medical University Drug resistance is currently an important issue facing targeted therapy for advanced NSCLC. median PFS for first-line treatment with TKI is about 10 months. Its drug resistance can be divided into primary resistance and secondary resistance. As the name implies, the former refers to TKI application without clinical benefit, while the latter refers to TKI application with clinical benefit, but the benefit is followed by tumor progression. Previously, the applicability of the efficacy evaluation criteria for solid tumors (RECIST) to the efficacy evaluation of targeted drugs was discussed in the clinical studies of sorafenib-targeted therapy for hepatocellular carcinoma. The same question exists today for the evaluation of TKI-targeted lung cancer: are the RECIST criteria based on imaging assessment applicable to TKI resistance? In the past, patients with NSCLC who developed drug resistance were often switched to another TKI, or chemotherapy, or chemotherapy followed by the original TKI.203 A study by Professor Yilong Wu et al. classified patients with drug resistance into three types, namely, burst progressive (disease control ≥ 3 months, rapid increase in tumor load compared to previous assessment, and symptom score of 2), slowly progressive (disease control ≥ 6 months, slight increase in tumor load compared to previous assessment), and slowly progressive (disease control ≥ 6 months, and tumor load compared to previous assessment). (disease control ≥ 6 months, slight increase in tumor load compared with previous assessment, symptom score ≤ 1), and locally progressive (disease control ≥ 3 months, rapid increase in tumor load compared with previous assessment, symptom score up to 2). Different treatments are recommended for the three progression patterns: switch to chemotherapy for the burst progression type, continue TKI drug therapy combined with chemotherapy for the slow progression type, and continue local treatment combined with TKI drugs for the local progression type. Of course, if tumor tissue specimens can be obtained again for testing after the emergence of drug resistance, we can use the appropriate individualized treatment for different resistance mechanisms: EGFR-TKI such as Afatinib for T790M irreversible; monoclonal antibodies for MET such as MetMab; drugs for insulin growth factor receptor (IGFR) pathway such as MK0646, AMG479, etc. Nevertheless, tumor tissue specimens for mutation testing are often not available. Currently, many patients with advanced disease are reluctant to undergo invasive testing to obtain tumor tissue specimens; sometimes patients cooperate but the tissue taken by fibrinoscopy fails to expand the target gene; some patients only have pleural fluid specimens; is it possible to do EGFR mutation testing in peripheral blood? Direct sequencing and fluorescence-based quantitative PCR assays (e.g. ARMS method) are currently recommended. Clinical studies have shown that DNA in pleural fluid can be used for EGFR mutation detection, but the detection of circulating free (cf) DNA in peripheral serum samples has a high false negative rate. For now, testing of the appropriate tumor material should be recommended whenever specimens are available. There are more questions worth exploring: 1. Why do patients with advanced NSCL CEGFR wild type benefit from second-line therapy when TKI cannot be applied in first line? 2. What other mechanisms exist for the application of TKI in 20-30% of patients with advanced NSCLCEGFR mutation type who are still insensitive to it? 3. The good quality of life in TKI treatment compared to chemotherapy makes me prefer TKI in first line, but there is no difference in overall survival between the two as long as they are both used, so how to use them better in combination with socioeconomic efficiency ratio and health insurance, so that patients not only benefit clinically but also have a more reasonable economic efficiency ratio.