Background. Trauma has a high incidence and mortality worldwide, and sepsis is one of the main causes of mortality in trauma patients. Therefore, it is essential to identify the risk factors of in-hospital mortality for trauma patients with sepsis. Methods. Data were extracted from the Medical Information Mart for Intensive Care III database and divided into a training set and internal validation set, and another Chinese dataset was used as external validation set. Then, risk factors were estimated using univariate and multivariate logistic regression analyses in the training set. Finally, a nomogram was created to predict the probability of in-hospital mortality for trauma patients with sepsis. Results. A total of 503 patients were enrolled in our study (335 in the training set and 168 in the validation set). Multivariate logistic regression analysis revealed that age (1.047 [1.025–1.071]), respiratory rate (1.258 [1.135–1.394]), PTT (1.026 [1.008–1.044]), ventilation (6.703 [1.528–29.408]), and vasopressor use (3.682 [1.502–9.025]) were independent factors associated with in-hospital mortality. The nomogram for trauma-related sepsis predicted in-hospital mortality with AUC values of 0.8939 in the training set, 0.8200 in the internal validation set, and 0.7779 in the external validation set. Conclusions. The new nomogram has a well predicted value for in-hospital mortality for patients with trauma and sepsis in intensive care units.