Background: Hyperfractionation (1.5Gy per dose twice a day, total dose 45Gy) or conventional fractionation (2Gy per dose once a day, total dose 60-70Gy) is the recommended dose fractionation for LS-SCLC. However, the optimal segmentation mode and dose of radiotherapy have not been determined. In this study, we evaluated the short-term efficacy and toxic and side effects of macrofractionation to explore the feasibility of macrofractionation radiotherapy in the treatment of LS-SCLC patients. Methods: From May 2011 to February 2020, 52 patients with LS-SCLC admitted to Jiangsu Cancer Hospital were retrospectively analyzed. The patients were divided into two groups according to the dose separation mode, including 29 cases in the large division group (3-4Gy per dose once a day, total dose 45-60Gy) and 23 cases (2Gy per dose once a day, total dose 50-68Gy) in the conventional division group. The short-term efficacy, 1-year survival rate and some other aspects of the two groups were compared. Results: The short-term overall response rate of large segmentation group was 79.3%, and there was significant difference compared with 52.2% of conventional segmentation group ( χ2 =4.293, P<0. 05) (Table). The 1-year survival rate of the large segmentation group was similar to that of the conventional segmentation group (82.8% vs．82.6%). The median survival time of large segment group was 30 months,which was not significantly different from the 34 months of conventional segment group (χ2=0.417, P>0.05). In terms of the effect of the two fractionated dose modes on long survival, 31.0% of patients in the large fractionation group survived more than 48 months, compared with only 13% in the conventional fractionation group. In addition, in the subgroup analysis of this study, it was found that compared with conventional fractionation radiotherapy, patients aged 45-65 years with ECOG score of 0-1 and lesions less than 5cm before radiotherapy could obtain more significant survival benefit from large fractionation radiotherapy, with statistically significant difference between the two groups (χ2=4.874, P<0.05). Conclusions: Large segmentation radiotherapy in the treatment of patients with LS-SCLC can improve the therapeutic effect and prolong the survival, especially for patients aged 45-65 years with ECOG score of 0-1 and lesions less than 5cm before radiotherapy , the survival benefit is more significant. In addition, large fractionated radiotherapy showed certain advantages in the long-term survival of patients with LS-SCLC, which is worthy of further clinical application.