The fibrosis-4 score is a marker of liver fibrosis and has been confirmed to be associated with the prognosis of various diseases. There is no study exploring the prognostic value of the fibrosis-4 score in traumatic brain injury (TBI) patients. We design this study to explore the association between the fibrosis-4 score and mortality from TBI. TBI patients from the Medical Information Mart for Intensive Care-III database were extracted for the study. Univariate and multivariate logistic regressions were sequentially performed to analyze the association between fibrosis-4 and mortality in TBI. The area under the receiver operating characteristic curve (AUC) was drawn to evaluate the prognostic value of fibrosis-4 and other scores. A total of 1018 TBI patients were included, with a 30-day mortality of 24.2%. Non-survivors had older age, lower Glasgow Coma Scale (GCS), and higher injury severity score (ISS) than survivors. The aspartate aminotransferase platelet ratio index (APRI) and fibrosis-4 score were significantly higher in non-survivors. Univariate logistic regression showed that age, GCS, ISS, white blood cell, hemoglobin, fibrosis-4 score, subarachnoid hemorrhage, and anticoagulants were associated with the mortality of TBI patients. Multivariate logistic regression presented that age, GCS, ISS, fibrosis-4 score, subarachnoid hemorrhage, and anticoagulants were independent risk factors of mortality in TBI patients after adjusting for confounding effects. The AUC of the GCS, ISS, APRI, and fibrosis-4 score for predicting mortality was 0.711, 0.625, 0.592, and 0.627, respectively. Composed of age, GCS, ISS, fibrosis-4 score, subarachnoid hemorrhage, and anticoagulants, the predictive model had the highest AUC value of 0.790. The fibrosis-4 score is an independent risk factor for mortality in TBI. The model incorporating fibrosis-4 performs well in predicting the prognosis of TBI patients.