Objective: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been recommended as the first-line treatment for advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutation. This study retrospectively evaluated patients’ survival and related prognostic factors from single-center, real-world data. Methods: From January 2015 to December 2020, patients detected with EGFR mutation showing unresectable clinical stages III to IV advanced lung adenocarcinoma and receiving EGFR-TKIs and radiotherapy (RT) were recruited for the study. The overall survival (OS) and progression-free survival (PFS) were statistically analyzed with SPSS 22.0 software. Results: This study included 238 patients who completed their follow-up by December 30, 2020. The 1-, 2-, 3-year and median OS were 84.4%, 59.7%, 38.7%, and 30.3 months for OS, 57.0%, 28.8%, 15.7%, and 14.1 months for progression-free survival (PFS1), and 78.9%, 71.7%, 33.3%, and 25.0 months for PFS2, respectively. Multivariate analysis showed that, the independent factors for OS are age, clinical stage, the sequence of TKI and CT, and the total treatment response, and total response; the independent factors for progression-free survival 1 are clinical stage and total treatment response; the independent factors for PFS2 are clinical stage, type of TKI, sequence of TKI and CT, and total treatment response. The univariate analysis also showed a significant association between RT duration ( P = 0.041) and dose ( P = 0.026) with PFS1. Conclusion: EGFR-TKIs combined with RT was tolerable and efficient for patients with advanced lung adenocarcinoma. OS and PFS prove CT sequential with TKIs. Better treatment response with CR + PR was associated with a longer duration of OS, PFS1, and PFS2. However, further study is required in a larger sample size to confirm the results.