Abstract: Objective To analyze the effect of hypo-fractionated conformal intensity-modulated radiotherapy (h-IMRT) on serum tumor markers and short-term efficacy in elderly patients with locally advanced NSCLC. Methods A total of 62 patients with advanced NSCLC who were treated from January 2018 to May 2020 were enrolled. They were randomly divided into two groups: an observation group and a control group. The observation group was intervened with hypo-fractionated conformal intensity-modulated radiotherapy, while the control group received conventional fractionated intensity-modulated radiotherapy. One month after treatment, the patients were evaluated for clinical efficacy according to RECIST 1.1 standard. The levels of serum CEA, CA125, CA19-9, and CYFRA21-1 were measured before and after treatment. Their adverse reactions was recorded. Results The objective remission rate of the observation group (80.64%) was better than that of the control group (45.16%), with statistical difference (χ²=8.627, P<0.05). There was no statistical difference in serum tumor markers between the two groups before treatment (P>0.05). After treatment, both groups showed remarkably reduced levels of serum CEA, CA125, CA19-9 and CYFRA21-1, compared with those before treatment (P<0.05). After treatment, the serum CYFRA21-1 level in the observation group was significantly lower than that in the control group (P<0.05). There was no statistical difference in the incidence of adverse reactions between the two groups after treatment (P>0.05). Conclusions The intervention of hypo-fractionated intensity-modulated radiotherapy in elderly patients with locally advanced NSCLC can significantly reduce the level of serum tumor markers and effectively improve the short-term curative effect.