AIM: To investigate the protective effect of ischemic preconditioning (IPC) on hepatocellular carcinoma (HCC)patients with cirrhosis undergoing hepatic resection under hepatic inflow occlusion (HIO) and its possible mechanism.METHODS: Twenty-nine consecutive patients with resectable 0HCC were randomized into two groups: IPC group: before HIO, IPC with 5 min of ischemia and 5 min of reperfusion was given; control group: no IPC was given. Liver functions,hepatic Caspase-3 activity, and apoptotic cells were compared between these two groups.RESULTS: On postoperative days (POD) 1, 3 and 7, the aspartate transaminase (AST) and alanine transaminase (ALT) levels in the IPC group were significantly lower than those in the control group (P＜0.05). On POD 3 and 7, the total bilirubin level in the IPC group was significantly lower than that in the control group (P＜0.05). On POD 1, the albumin level in the IPC group was higher than that in the control group (P = 0.053). After 1 h of reperfusion, both hepatic Caspase-3 activity and apoptotic sinusoidal endothelial cells in the IPC group were significantly lower than those in the control group (P＜0.05).CONCLUSION: IPC has a potential protective effect on HCC patients with cirrhosis. Its protective mechanism underlying the suppression of sinusoidal endothelial cell apoptosis is achieved by inhibiting Caspase-3 activity.