Objective To evaluate the predictive value of intestinal fatty acid-binding protein (I-FABP) in the prognosis of patients with liver cirrhosis. Methods A prospective study method was used to continuously collect patients with liver cirrhosis, who were hospitalized in a hospital from September 2020 to May 2022. Patients were stratified according to the Child-Pugh score, and followed up 12 months to evaluate their survival and bacterial infection. Serum I-FABP level of patients at admission was measured by enzyme-linked immunosorbent assary (ELISA). The correlation between two variables was analyzed by Spearman correlation analysis. Risk factors for bacterial infection and death during follow-up was predicted with multivariate Cox regression model. Predictive efficacy of I-FABP for cirrhosis-related death was evaluated with time-dependent receiver operating characteristic (ROC) curve. Results A total of 131 patients with liver cirrhosis were included. During the follow-up period, 45 patients were hospitalized due to bacterial infection or infection progress. The median length of hospital stay due to infection was 115 (42, 251) days, and the average length of hospital stay was 15 days. The most common infection is spontaneous bacterial peritonitis (SBP), accounting for 20.6% (n=27). I-FABP was correlated with serum IL-6 (r=0.270, P < 0.001) and MELD score (r=0.364, P < 0.001), and increased with the severity of the disease (Child-Pugh A=1.18 μg/L, Child-Pugh B=1.51 μg/L and C=2.29 μg/L). During the follow-up period, 45 patients (34.4%) were hospitalized for 71 times due to bacterial infection. The median I-FABP of 27 patients with SBP was higher than those without SBP (2.26 vs 1.25, P=0.001). In addition, 29 patients died during the observation period. The mortality at 3 months, 6 months, 9 months and 12 months were 4.6%, 13.7%, 19.8% and 22.1%, respectively. Multivariate Cox regression analysis showed that baseline I-FABP could predict SBP and 1-year survival rate, and the I-FABP quartile showed good prognostic differentiation. Time-dependent AUC showed no difference in predicting mortality of liver-related death between I-FABP and MELD score. The combined model of the two parameters showed a high predictive value. Conclusion I-FABP can predict the occurrence of cirrhosis-associated SBP and the long-term survival in patients with liver cirrhosis.