Abstract: Objective To evaluate the effects of substantial late course X-knife radiotherapy on local advanced non-small lung cancer (NSCLC) without progression after four cycles of docetaxel plus cisplatin (DP regimen), and to observe adverse events. Methods A total of 57 NSCLC patientswho received four cycles of DP regimen without disease progression were randomly divided into two groups.The first group includes the patients in conventional radiotherapy group receiving conventional fractionated radiotherapy by 2 Gy/fraction, 1 fraction/day, 5 fractions/week to a total dose of 64 Gy.The other includes those in X-knife group received conventional radiotherapy for 4 weeks with the same schedule as conventional radiotherapy group, then received X-knife radiotherapy by 6 Gy/fraction, 3 fractions/week to a total dose of 76 Gy. The responses and adverse events between these two groups were compared. Results The complete remission (CR) rate was significantly higher in X-knife group than in conventional radiotherapy group (38.7% vs. 15.4%, P=0.047). The 3-year survival rate was also significantly higher in X-knife group than in conventional radiotherapy group (35.5% vs. 15.4%, P=0.035). There was no significant difference in the occurrence of adverse events between these two groups. Conclusion Comparing with conventional radiotherapy, substantial late course X-knife radiotherapy could improve complete remission and long-term survival of local advanced NSCLC patients without progression after chemotherapy, without increasing adverse events; it can be recommended as standard treatment for local advanced NSCLC.