Objective To comparatively evaluate the clinical efficacy and adverse events of chemoradiotherapy combined with/without radioactive iodine-125 ( 125-I) implantation for locally advanced non-small cell lung cancer. Methods With locally advanced non-small cell lung cancer admitted to Department of Radiotherapy of Jianhu County People's Hospital and Yancheng Third People's Hospital from March 2014 to March 2015 of 38 patients were enrolled and randomly divided into the observation ( chemoradiotherapy+ radioactive 125-I implantation, n=20) and control groups ( chemoradiotherapy, n=18) . All patients underwent conventional three-dimensional conformal radiotherapy and TC chemotherapy. In the observation group, 125-I implantation was performed at 3 months after chemoradiotherapy. The short-term clinical efficacy, progression-free survival, overall survival and adverse events were statistically compared between two groups. Results The total effective rate in the observation group was 85%, significantly higher than 56% in the control group ( P=0.046) . Until May, 2018, the progression-free survival rates in the observation and control groups were 65% and 61% ( P=0.457) , the overall survival rates were 32% and 26%, and the median survival time was 22.8( 95%CI: 20.5-23.5) and 21.3( 95%CI: 15.9-26.0) months ( P=0.633) . The incidence rates of adverse events in the observation and control groups were 45% and 78% ( P>0.05) . Conclusions Concurrent chemoradiotherapy combined with radioactive 125-I implantation yields high short-term efficacy in the treatment of locally advanced non-small cell lung cancer. It can prolong the long-term survival to certain extent and yield a low incidence rate of severe adverse events, which deserves to be validated by large sample-size investigations.