The aim of this study was to analyze the efficacy according to EGFR status and predictors of TKIs in Chinese advanced lung adenocarcinoma patients in a single institute. We retrospectively enrolled 253 patients with advanced or recurrent adenocarcinoma and history of EGFR-TKI treatment attended at Beijing Chest Hospital in Beijing, China, from July 2007 to August 2012. Overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were analyzed according to EGFR status and in different treatment lines. The predictors of outcomes were also evaluated. Of all of the patients, the ORR was 36.0%, DCR was 66.0%, the median PFS time was 6.0 months, and the median OS time was 14.2 months. Compared with patients with EGFR wild type and EGFR status unknown, the ORR and PFS in patients with EGFR-activating mutations were significantly better (p < 0.001, p < 0.001; p < 0.001, p = 0.004, respectively). In patients harboring activating mutations, the ORR in first line and second line or beyond were 62.1%, 54.3%; DCR were 79.3%, 89.1%; PFS were 8.7 months and 7.8 months (p = 0.633, 0319, 0.320, respectively). The multivariate analysis showed that EGFR mutations and nonsmoking were independent factors of better ORR. In Cox regression analysis, ECOG performance status (PS) 0-1, nonsmoking, low number of metastatic organs, EGFR-activating mutations were independent factors of longer PFS. ECOG PS 0-1 and low number of metastatic organs were independent factors of longer OS. In conclusion, patients harboring EGFR-activating mutations had better ORR and longer PFS in TKI treatment. There was no difference in the ORR and PFS in patients with activating mutations in the first line and the second line or beyond.