Objective To establish a nomogram of national early warning score (NEWS) combined with relevant indicators to predict the prognosis of patients with sepsis, so as to provide clinicians with a more accurate prediction model and improve the prognosis of patients with sepsis. Methods Clinical data of patients with sepsis who admitted to emergency intensive care unit (EICU), surgical intensive care unit (SICU) and medical intensive care unit (MICU) of a hospital from January 2019 to December 2021 were retrospectively collected, those who met the inclusion criteria were randomly divided into test group and verification group. In test group, patients in death group and survival group were analyzed by univariate and multivariate analysis, differences in clinical manifestations and laboratory indicators between two groups of patients were compared, the nomogram was constructed based on its independent risk factors, the accuracy was verified. Results A total of 330 patients were finally included in analysis, there was no significant difference in the baseline data between test group and verification group (all P>0.05). Univariate and multivariate analysis results of death group and survival group in test group showed that NEWS (OR=1.70, 95%CI: 1.36-2.14), combined with respiratory failure (OR=3.82, 95%CI: 1.13-12.92), ventilator use during disease course (OR=0.26, 95%CI: 0.09-0.80), red blood cell distribution width (OR=1.25, 95%CI: 1.05-1.50), and lactic acid value (OR=1.55, 95%CI: 1.27-1.91) were independent risk factors affecting the 30-day prognosis of patients with sepsis. The nomogram model for evaluation and validation of prognosis showed that the C-index of test group and validation group were 0.903 and 0.905 respectively, the calibration curves between two groups fit well with the ideal curve, and the areas under receiver operating characteristic curve were 0.916 and 0.899 respectively, indicating that the model has good prediction efficiency. Decision curve analysis showed that nomogram had high clinical benefit in test group and validation group. Conclusion There are multiple relevant factors affecting the prognosis of patients with sepsis, combined with the most valuable influencing factors, a nomogram for predicting the prognosis of patients with sepsis based on NEWS has good prediction performance, which can further provide clinicians with a simple and effective evaluation method, improve the prediction accuracy.