A 48-year-old male with EGFR-positive non-small cell lung cancer (NSCLC), presented with chest tightness, chest pain, and shortness of breath for the past two weeks was admitted into the Shanghai Chest Hospital on June 16, 2015. Chest CT showed multiple nodules on the right pleura, shadow in the right lower lobe, and right-sided pleural effusion. Pathological and histochemical analysis of pleural effusion suggested lung adenocarcinoma. The genetic test showed EGFR 19 exon deletion mutation (19del). The patient was diagnosed with advanced EGFR-mutated lung adenocarcinoma and treated with standard platinum-based chemotherapy combined with EGFR-TKIs as the first-line regimen followed by pemetrexed and gefitinib as a maintenance therapy. Partial regression (PR) was observed and progression-free survival (PFS) achieved 15 months for the first-line. Bevacizumab was additionally administered in the second-line and stable disease (SD) with a PFS of 18 months were observed. EGFR 790 mutation was displayed after disease progression. The third-line treatment was composed of third-generation EGFR-TKIs and bevacizumab. Chest CT showed a complete regression (CR) and the patient is still under follow-up. The overall survival (OS) has exceeded 50 months. Combination therapy provides survival benefit in the treatment of advanced EGFR-mutated NSCLC.