Objective To investigate the effect of blood lipids on the survival prognosis of intermediate and advanced non-small cell lung cancer NSCLC radiotherapy patients. Method A retrospective analysis was performed on the clinical data of 164 patients with stage Ⅲ to Ⅳ NSCLC and dyslipidemia who received radiotherapy at Sichuan Cancer Hospital from January 2018 to May 2023. The optimal cutoff values for total cholesterol TC and triglyceride TG were determined using the receiver operating characteristic ROC curve with subsequent stratification of patients into corresponding groups. Prognostic factors were evaluated using both univariate and multivariate Cox regression models complemented by Kaplan-Meier survival analysis for statistical comparisons and clinical outcome assessment. Result The ROC curve was used to obtain the optimal cut-off values of cholesterol and triglycerides and the optimal cut-off values of TC and TG were 5. 72 mmol / L and 1. 795 mmol / L respectively. The DCR of the low cholesterol group < 5. 72 mmol / L was significantly higher than that of the high cholesterol group ≥5. 72 mmol / L P<0. 05 . Median progress free survive PFS in the low- cholesterol group was significantly better than that in the high - value group 16 vs 12 months P = 0. 0078 . However there was no statistically significant difference in median overall survival OS between the two groups 44 months vs 36 months P= 0. 1681 . Compared with the non-use group the mPFS 18 months vs 11 months P= 0. 014 and OS 54 vs 35 months P= 0. 027 were significantly longer in the lipid-lowering drug group. The mPFS 16 months of patients with decreased cholesterol levels after radiotherapy was 7 months longer than that of patients with increased cholesterol 9 months P= 0. 0215 and the OS 41 months vs 38 months was 3 months longer P = 0. 2700 . Cox multifactorial analysis suggested that tumor stage cholesterol level,trend of cholesterol change after radiotherapy and total protein were risk factors for NSCLC prognosis P < 0. 05 . Conclusion Tumor stage cholesterol level and its trend and total protein level are independent prognostic factors affecting patients with NSCLC. Pre-radiotherapy cholesterol level and the use of lipid - lowering drugs can significantly improve PFS and OS in patients with dyslipidemia undergoing radiotherapy for intermediate and advanced NSCLC and have the potential to improve survival outcomes.