The occurrence of acute kidney injury (AKI) in acute-on-chronic liver failure (ACLF) negatively impacts the survival of patients. There are scant data on the impact of serum urea on outcomes in these patients. We performed this study to evaluate the relationship between admission serum urea and the survival in patients with ACLF and AKI. A prospective study was conducted on patients with ACLF (as per Asian Pacific Association for the Study of the Liver criteria) and AKI (as per Acute Kidney Injury Network criteria) hospitalized in the gastroenterology ward between October 2016 and May 2018. Demographic, clinical and laboratory parameters were recorded, and outcomes were compared in patients with respect to the admission serum urea level. A total of 103 of 143 hospitalized patients with ACLF had AKIand were included as study subjects. The discrimination ability between survivors and the deceased was similar for serum urea levels (area under the receiver operating characteristic curve [AUROC] [95% confidence interval {CI}]: 28 days survival, 0.76 [0.67-0.85]; 90 days survival, 0.81 [0.72-0.91]) and serum creatinine levels (AUROC [95% CI]: 28 days survival, 0.75 [0.66-0.84]; 90 days survival: 0.77 [0.67-0.88]) in patients with ACLF and AKI. However, on multivariate analysis, admission serum urea (not serum creatinine) was an independent predictor of mortality in these patients both at 28 days (p= 0.001, adjusted hazard ratio [AHR]: 1.013 [1.005-1.021]) and 90 days (p= 0.001, AHR: 1.014 [1.006-1.022]). Over two-thirds of patients with ACLF had AKI. The discrimination ability between survivors and the deceased was similar for both serum urea and serum creatinine levels. However admission serum urea was found to be a better predictor of mortality than serum creatinine in patients with ACLF and AKI.