OBJECTIVE: To observe the efficacy and adverse effects of radiotherapy combined with thermotherapy in the treatment of locally advanced non-small cell lung cancer (NSCLC). METHODS: Seventy patients who met the enrollment criteria were randomly divided into radiotherapy alone group (30 patients) and radiotherapy combined with thermotherapy group (40 patients). Both groups received MLC radiotherapy at 50-60Gy/25-30f/5-6w, and in the radiotherapy combined with heat therapy group, they received heat therapy at the same time during radiotherapy for a total of 14 times and 18 times (median number of heat therapy sessions was 15). RESULTS: The efficiency and 1-year local control rate of the radiotherapy combined with heat therapy group were higher than those of the radiotherapy alone group (80.O% vs 53.3%, P0.05; 54.4% vs 56.7%, P>0.05), and all of them were mainly grade I and grade II injuries. 3.Discussion Radiotherapy has a significant position in the treatment of locally advanced non-small cell lung cancer, and the tumor size directly affects the efficacy of radiotherapy. For larger tumors, the lack of angiogenesis puts the cells inside the tumor in a state of low pH, lack of oxygen and lack of nutrients, and there is obvious radiation resistance, which affects the efficacy of radiotherapy. Tumor cells that are not sensitive to radiotherapy, especially hypoxic cells and S-phase cells, are hypersensitive to thermotherapy. The rational application of heat therapy and radiotherapy can complement each other and synergistically increase sensitivity. The anti-tumor mechanism of heat therapy: (1) direct killing effect on tumor cells; (2) anti-tumor vascular effect; (3) tumor apoptosis; (4) up-regulation of the body’s immune function; (5) inhibition of tumor invasion; (6) molecular biology mechanism: inhibition of DNA and RNA synthesis and polymerization of tumor cells, resulting in irreversible damage. Heat therapy and radiotherapy have synergistic and sensitizing effects. The mechanisms are: (1) central tumor cells are in hypoxic and low pH state, resistant to radiation and easily killed by high heat; tumor margins have good blood transport and sufficient blood oxygen, not sensitive to heat, but sensitive to radiation. The S-phase cells, which are resistant to radiation, are sensitive to heat. ③Heating can increase blood circulation, increase the oxygen content of cells in the tumor, and increase the sensitivity to radiation. ④Heat therapy inhibits the repair of cellular radioactive damage. The combined application of thermotherapy and radiotherapy can significantly improve the effect of tumor radiotherapy with mild side effects. In conclusion, for patients with locally advanced NSCLC, radiotherapy combined with thermotherapy is a safe and effective treatment that deserves further exploration.