AIM: A high prevalence of overestimated renal function in patients with liver cirrhosis (LC) has been reported; nonetheless, its impact on prognosis remains unclear. We aimed to evaluate the impact of overestimated renal function on prognosis in patients with LC. METHODS: An overestimated renal function was defined as a >20% increase in the creatinine-based estimated glomerular filtration rate (eGFR), compared with cystatin C-based eGFR. LC patients with conserved serum, who were evaluated for muscle atrophy and had proper clinical information were included, and their prognostic factors were analyzed. RESULTS: A total of 215 consecutive patients with LC were included. The prevalence of overestimated renal function was 29.8% (64/215). Kaplan-Meier survival analysis revealed that patients with overestimated renal function had a poorer prognosis than those without overestimated renal function (hazard ratio [HR]: 2.217 95% confidence interval [CI]: 1.290-3.810; P=0.001). Subgroup analysis showed that overestimated renal function was a significant prognostic factor, irrespective of sex and the presence of hepatocellular carcinoma (HCC). Multivariate Cox regression analyses revealed that overestimated renal function was a significant and independent factor predictive of poor prognosis in the entire cohort (HR: 2.050; 95% CI: 1.041-4.037; P=0.038) and in subgroups classified by Child-Pugh class A (HR: 2.131; 95% CI: 1.019-4.458; P=0.044), Model for End-Stage Liver Disease score <9 (HR: 2.303; 95% CI: 1.038-5.109; P=0.04), and presence of HCC (HR: 2.290; 95% CI: 1.128-4.651; P=0.022). CONCLUSION: Overestimated renal function is a significant and independent prognostic factor in patients with LC. This article is protected by copyright. All rights reserved.