Objective To investigate the effect of neutrophil-to-lymphocyte ratio (NLR) combined with sequential organ failure assessment (SOFA) score on the prognosis of the elderly patients with sepsis. Methods Clinical data of 124 elderly patients with sepsis admitted in Chinese PLA Hospital No.305 from January 2017 to August 2019 were collected and retrospectively analyzed. According to the prognosis, they were divided into survival group (n=58) and death group (n=66). Their sex, age, underlying diseases, primary disease, NLR and SOFA scores were compared between two groups. Multivariate logistic regression analysis was used to explore the risk factors affecting the prognosis. Receiver operating characteristic (ROC) curve was plotted to assess the predictive values of the risk factors for the elderly patients with sepsis. Results There were no significant differences in gender ratio, age, underlying diseases and primary disease between two groups. But, the NLR and SOFA scores in the survival group were significantly lower than those in the death group (P<0.001). Multivariate logistic regression analysis indicated that NLR (OR=1.163,95%CI 1.090－1.241, P<0.001) and SOFA scores (OR=1.406,95%CI 1.199－1.649, P<0.001) were independent risk factors for the prognosis of elderly sepsis patients. The area under ROC curve (AUC) of NLR was 0.918 (95%CI 0.872－0.964, P<0.001), and the cut-off value was 30.68 (sensitivity 86.2%, specificity 81.8%). The AUC of SOFA score was 0.844 (95%CI 0.771－0.916, P<0.001), and the cut-off value was 12.5 (sensitivity 81.0%, specificity 80.3%). However, AUC of their combination was 0.964 (P<0.001), which was better than either of them. Conclusion NLR and SOFA scores are the risk factors of death in the elderly patients with sepsis. Their combination can greatly improve the accuracy of prognosis estimation and provide guidance in clinical practice.