Objective To study the short-term outcome and safety of radiofrequency ablation (RFA) combined with recombinant human endostatin (endostar) for non-small cell lung cancer (NSCLC) patients. Methods Between December 2013 and December 2014, 80 consecutive patients (50 males, 30 females) with biopsy-proved NSCLC were divided into two groups: a RFA combined treatment group (RFA combined with endostar, 60 patients, 38 males, 22 females, mean age at 67.77±10.43 years) and a RFA alone group (20 patients, 12 males, 8 females, mean age at 67.35±9.82 years). The RFA combined treatment group was divided into three groups according to vascular normalization window of endostar and 20 patients in each group: a combined treatment group 1 (transfusion of endostar after RFA), a combined treatment group 2 (transfusion of endostar for 1 to 3 d before RFA) and a combined treatment group 3 (transfusion of endostar for 4 to 7 d before RFA). The CT scan of the chest was followed up after the treatment, local recurrence and safety was observed. Results There was a statistical difference in local recurrence time among groups (χ2 = 11.05, P = 0.011). The effect of the combined treatment group is better than that of the radiofrequency ablation therapy alone group. And in the recombinant human endostatin of tumor vascular normalization time best combination therapy was observed in the near future effect compared with the radiofrequency ablation therapy alone. In this study common complications were associated with radiofrequency ablation. No recombinant human endostatin related complication was found. There was no satistical difference in safety between the combined treatment group and the radiofrequency ablation therapy group (χ2= 0.889, P > 0.05). Conclusion RFA combined with endostar is safe and effective for non-small cell lung cancer.