Objective: To compare the effects of different radiotherapy regimens on the survival status and serum tumor markers in patients with brain metastasis of lung cancer. Methods: 98 patients with brain metastasis of lung cancer admitted to our hospital from May 2022 to July 2023 were selected and divided into control group [ whole brain radiation therapy ( WBRT ) + sequential tumor bed boost intensity-modulated radiotherapy, n = 47 ] and observation group ( WBRT + synchronous tumor bed boost intensity-modulated radiotherapy, n = 51 ) according to different treatment regimens. The clinical efficacy, 1-year survival rate, disease progression, tumor markers [ cytokeratin fragment 19 ( CYFRA21-1 ), squamous cell carcinoma antigen ( SCC ), carcinoembryonic antigen ( CEA ) ] levels and adverse reactions were compared between the two groups. Results: After treatment, the objective remission rate and disease control rate of the observation group were higher than those of the control group (88.24% vs 59.57%, 96.08% vs 80.85%, P<0.05); The one-year survival rate of the observation group was higher than that of the control group (68.63% vs 44.68%, P<0.05); After treatment, there was no significant difference in disease progression between the observation group and the control group, including pulmonary progression, new extracranial metastases, both intracranial and extracranial progression, only extracranial progression, and only intracranial progression (39.22% vs 44.68%, 1.96% vs 6.38%, 0.00% vs 2.13%, 41.18% vs 51.06%, 3.92% vs 12.77%, all P>0.05); After treatment, the levels of CYFRA21-1, SCC and CEA in the two groups decreased, and the levels in the observation group were lower than those in the control group [ (2.98 ± 0.37) U·mL-1 vs (4.16 ± 0.53) U·mL-1, (1.61 ± 0.23) μ g·L-1 vs. LVS (2.05 ± 0.42) μ g·L-1, (16.22 ± 1.89) ng·mL vs. LVS (20.96 ± 3.86) ng·mL-1, P < 0.05 ].The adverse reactions of the two groups of patients after radiotherapy were tolerable, and there was no significant difference between the control group and the observation group in adverse reactions including nausea and vomiting, dizziness, memory impairment, cognitive impairment, and bone marrow suppression (70.59% vs 72.34%, 25.49% vs 36.17%, 35.29% vs 44.68%, 27.45% vs 25.53%, 21.57% vs 29.79%, P>0.05). Conclusion: Compared with sequential tumor bed boost intensity-modulated radiation therapy, whole brain synchronous boost intensity-modulated radiation therapy is more effective, which can improve the 1-year survival rate of patients and reduce the level of tumor markers.