Objective To assess the value of acute gastrointestinal injury (AGI) and intestinal fatty acid-binding protein (I-FABP) in the prognosis of liver cirrhotic patients with sepsis. Methods Clinical data of 84 liver cirrhosis patients with sepsis who were admitted to the intensive care unit (ICU) of a hospital from September 2020 to March 2023 were analyzed retrospectively, and 41 patients with decompensated liver cirrhosis during the same period were selected as the control group. Serum I-FABP level in patients was determined with enzyme-linked immunosorbent assay (ELISA). Scores of the model of end-stage liver disease (MELD) and sequential organ failure assessment (SOFA) were calculated. AGI was evaluated based on medical records. 30-day and 90-day survival was observed. Correlation among variables was analyzed by Spearman correlation. Risk factors for death in patients with liver cirrhosis and sepsis was determined by multivariate Cox regression analysis. The optimal cut-off value was determined by receiver operating characteristic (ROC) curve, and the diagnostic efficacy was compared through the area under the ROC curve (AUC). Results Both AGI grading and I-FABP level in liver cirrhosis patients with sepsis were higher than those in the control group (both P < 0.05). I-FABP level was correlated with procalcitonin (PCT), MELD, and SOFA scores in patients with liver cirrhosis and sepsis (all P < 0.05). AGI grading was positively correlated with SOFA score (P=0.038). The 30-day and 90-day mortality of patients in the liver cirrhosis with sepsis group were 25.0% (n=21) and 35.7% (n=30), respectively. Multivariate Cox regression analysis showed that baseline I-FABP and SOFA scores were independently correlated with 30-day and 90-day survival, and the I-FABP quartile showed good prognostic differentiation efficacy. ROC curve showed that I-FABP could significantly improve the predictive effect of SOFA score on the prognosis of patients. Conclusion AGI grading and I-FABP level in liver cirrhosis patients with sepsis are elevated significantly. Serum I-FABP is associated with the prognosis of patient and can improve the predictive efficacy of SOFA score for survival.