Abstract: Objective: To investigate the value of the detection of epidermal growth factor receptor(EGFR) gene mutation in pleural effusion of patients with advanced non-small cell lung cell(NSCLC) in predicting the curative effect of Erlotinib.Methods: The EGFR gene mutation in pleural effusion of 275 patients with NSCLC were detected using PCR-HRM,and 52 tissue samples were detected using HRM and direct sequencing.The consistency and repeatability of EGFR mutation in pleural effusion and tissue specimens were compared,respectively.The EGFR mutation sensitive patients were randomly treated with the erlotinib or gemcitabine cisplatin therapy.The objective response rate(ORR) and median progression-free survival(mPFS) between two groups were compared.Results: The sensitive mutation rate of EGFR in pleural effusion of 275 NSCLC patients was 55.3%.Among the pairing tissue specimens and pleural effusion of 52 cases,the sensitive mutation rate of EGFR was 61.5%,which was higher than that using the direct sequencing(40.3%)(P<0.01).The sensitive mutation rate of EGFR in pleural effusion was 55.8%,which was higher than that using direct sequencing(36.5%)(P<0.01).The coincidence rate of the EGFR mutation in tissue specimen and pleural effusion was 82.6%.The mPFS in Erlotinib group was 11.5 months(95%CI for 10.4 to 12.6),which was higher than 4.4 months in GP group(95%CI for 3.9 to 4.8)(P<0.01).The ORR in Erlotinib group(70.0%) was significantly higher than that in GP group(29.4%)(P<0.01).Conclusions: Among the patients with advance NSCLC,the sensitive mutation detection of EGFR in pleural effusion can compensate or replace the detection of tissue specimens,and the sensibility of HRM is better than that of direct sequencing.The application of Erlotinib in NSCLC patients with EGFR sensitive mutation can improve the ORR,and prolong mPFS.