Objective: To evaluate the clinical value of Endostar combined with targeted therapy [epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), Iressa, or Tarceva] in the treatment of advanced elderly non-small cell lung cancer (NSCLC). Methods: Ninety patients with advanced NSCLC who met the enrollment conditions were all tested for EGFR (19, L858 mutation). 45 patients were given oral Iressa 250 mg qd or Tarceva 150 mg, once a day orally, and 30 mg, once a day of Endostar were administered as intravenous drip (d1–7), a comparative analysis was performed with 45 elderly patients with advanced NSCLC who received EGFR-TKI alone as a control group. Results: Forty-five patients in the combined drug group evaluated the efficacy, and the disease control rate (DCR) rate was significantly higher than that in the control group, and the difference was statistically significant (P<0.05). The improvement in quality of life was significantly better than that in the control group, and the difference was statistically significant (P<0.05). In addition, patients were tolerable to adverse reactions such as rash and diarrhea. Conclusion: First-line application of Endostar combined with EGFR-TKI has high disease control rate, improved quality of life, and tolerable side effects.