Research has previously been done into the risk factors for mortality in septic shock patients. However, there has been no epidemiological study investigating the effect of the blood urea nitrogen/creatinine ratio (BCR) on the prognosis of critically ill septic shock patients. This study is aimed at determining the relationship between BCR and all-cause mortality in adult septic shock patients.Data were extracted from the MIMIC-III database. The clinical endpoints were 28-, 90-, and 365-day all-cause mortality rates in critically ill septic shock patients. Cox proportional hazards models and subgroup analyses were used to analyze the relationship between BCR quartiles and all-cause mortality in septic shock patients. Receiver operator characteristic (ROC) curves and areas under the ROC curves (AUCs) were calculated to evaluate how accurately BCR predicts the mortality of septic shock patients.Among the 2484 septic shock patients extracted from the database, 619, 563, 677, and 625 fell into the first (<14.4 mg/dL), second (≥14.4 mg/dL and <20.0 mg/dL), third (≥20.0 mg/dL and <27.3 mg/dL), and fourth (≥27.3 mg/dL) quartiles of BCR, respectively. Male and white patients accounted for 53.8% (1336 patients) and 74.8% (1857 patients) of the population, respectively. The mean age of the population was 67.7 ± 15.8 years. An inverse M-shaped relationship between BCR and mortality in septic shock patients was identified, with a value of ≥27.3 mg/dL providing the highest risk (HR = 1.596, 95% CI: 1.396-1.824, P < 0.001). In the Cox regression model adjusted for different confounding variables, BCR values in the fourth quartiles were significantly associated with increased mortality, using the first quartiles as a reference. The areas under the ROC curves (AUCs) for BCR plus the Sequential Organ Failure Assessment (SOFA) score and BCR plus Acute Physiology Score III (APSIII) were 0.694 (95% CI: 0.673-0.716) and 0.724 (95% CI: 0.703-0.744), respectively.An inverse M-shaped curve was determined between BCR and the mortality of septic shock patients. BCR was identified as a readily available and independent prognostic biomarker for septic shock patients, and higher BCRs were associated with increased mortality in these patients.Copyright © 2021 Didi Han et al.