Objective: To investigate the effects of three-dimensional conformal radiotherapy (3D-CRT) and static intensity-modulated radiotherapy (IMRT) on locally advanced non-small cell lung cancer (NSCLC). Method: 96 patients with locally advanced NSCLC admitted to our hospital from January 2023 to December 2024 were selected as the research subjects. The patients were divided into the 3D-CRT group (n=48) and the IMRT group (n=48) according to the random number table method. The 3D-CRT group was treated with 3D-CRT. The IMRT group was treated with IMRT. The therapeutic effects, dosimetric parameters, tumor marker levels [carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125)] and the incidence of adverse reactions of the two groups were analyzed and compared. Result: There was no significant difference in the total effective rate between the two groups (P > 0.05). Compared with the 3D-CRT group, the heterogeneity index and conformal index of the IMRT group were significantly increased (P < 0.05). However, there was no significant difference in the average dose between the two groups (P > 0.05). After treatment, the levels of CEA and CA125 in both groups were significantly lower than those before treatment, and the levels of CEA and CA125 in the IMRT group were significantly lower than those in the 3D-CRT group (P < 0.05). The incidences of radiation esophagitis, leukopenia, radiation pneumonitis and bone marrow suppression in the IMRT group were significantly lower than those in the 3D-CRT group (P < 0.05). Conclusion: The efficacy of 3D-CRT and IMRT in the treatment of locally advanced NSCLC is comparable. However, compared with 3D-CRT, IMRT can significantly increase the heterogeneity index and conformance index of tumor target areas, reduce the levels of tumor markers, and decrease the occurrence of adverse reactions such as radiation esophagitis and leukopenia.