Abstract: Objective To investigate the clinical characteristics of acquired resistance of epidermal growth factor receptor （EGFR） sensitive mutation in patients with advanced lung adenocarcinoma treated with first-line EGFR-tyrosine kinase inhibitor（EGFR-TKI）therapy. Methods A total of 193 patients with advanced lung adenocarcinoma bearing EGFR sensitive mutation were enrolled from January 2011 to December 2015， and 120 patients of them were given the first-line EGFR-TKI therapy. The relationship of short-term efficacy， as well as EGFR mutation types and locations of tumor progression was analyzed. Results No complete remission （CR） was observed in 120 patients receiving the first-line EGFR-TKI treatment. Eighty patients （66.7％） achieved partial remission （PR） and the median progression-free survival （PFS） was 12.1 months. Thirty-six patients （30.0％） achieved stable disease （SD） and the median PFS was 6.1 months. The difference of PFS between them had statistical significance （P＜0.05）. Among patients achieved PR and SD， the exon 19 deletions was found in 64 cases （55.2％） and the median PFS was 11.0 months. The mutation of L858R occurred in 52 cases （44.8％） and the median PFS was 8.6 months， the differences between PFS also had statistical significance （P＜0.05）. Fifty cases （43.1％） with acquired resistance only had progresses in original lesions， and 66 patients （56.9％） were found new lesion metastases. At the time of disease progression， lung progression accounted for 37.9％， followed by brain metastases accounted for 26.7％. Clincial efficacy （PR／SD） and EGFR mutation （exon 19 deletions／L858R mutations） were not related to location of tumor progression and original/new lesions（P＞0.05）. Conclusion Lung is the most common locations of tumor progression after acquired resistance to EGFR-TKI in patients with EGFR mutation， followed by brain metastases. The location of tumor progression and clinical efficacy， as well as EGFR mutation genotypes are not exactly related.