Objective To explore the risk factors associated with acute liver injury in patients with hepatocellular carcinoma （HCC） following hepatic artery chemoembolization （cTACE）. Methods A retrospective analysis was conducted on the clinical data of 252 HCC patients who received cTACE treatment at the Affiliated Hospital of Xuzhou Medical University and Xuzhou Central Hospital from January 2024 to July 2025. The patients were divided into an acute liver injury group and a non-acute liver injury group based on whether acute liver injury occurred after surgery. Independent risk factors were screened through multiple logistic regression analysis. Results Multivariate analysis indicated that giant hepatocellular carcinoma， Child-Pugh B grade， combined cirrhosis， TACE frequency greater than 2 times， preoperative albumin （ALB） less than 30 g/L， an increase in the preoperative fibrosis factor 4 index （FIB-4）， an increase in the preoperative neutrophil/lymphocyte ratio （NLR）， an increase in the preoperative platelet count index （APRI）， and a decrease in the postoperative liver volume （LV） were all independent risk factors for acute liver injury in HCC patients undergoing cTACE （all P < 0.05）. ROC curve analysis demonstrated that the areas under the curve （AUC） for predicting acute liver injury after cTACE by preoperative FIB-4， NLR， APRI， and postoperative LV were 0.786， 0.704， 0.816， and 0.847， respectively； The sensitivities were 0.716， 0.672， 0.761， and 0.821， respectively； The specificities were 0.708， 0.701， 0.805， and 0.836， respectively. Conclusions The occurrence of acute liver injury after cTACE in HCC patients is influenced by factors including massive HCC， Child-Pugh class B， concurrent liver cirrhosis， more than 2 TACE sessions， preoperative ALB < 30 g/L， preoperative FIB-4， preoperative NLR， preoperative APRI， and postoperative LV.