Abstract: Objective To assess the value of clinical application of i sc hemic preconditioning (IP) before hepatic vascular ex-clusion for resection of h epatocellular carcinoma (HCC) accompanied by cirrhosis and explore the possible mechanism under-lying the protective effect of this maneuver.Methods Thirty-four consecutive patients with resectable HCC were randomized into IP group to receive IP with a 5-min ischemia followed by 5-min perfusion before hepatic vascula r exclusion and the con-trol group with simply hepatic vascular exclusion. The liver function, hepatic Fas mRNA expression, caspase-3 activity, apop-tosis of th e hepatocytes were compared between the two groups.Results In the IP group, the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels on p ostoperative day 1, 3 and 7 were all significantly higher than those of the con trol group (t=6.985, P<0.01). The total bilirubin levels were also higher in the former group on postoperative day 3 and 7 (t=3.447, P<0.05). The IP group had h igher albumin levels on postoperative day 1 than the control group (t=3.360, P<0 .05). After 1 hour’s reperfusion, the hepatic mRNA expression of Fas, caspase-3 activity and apoptotic sinusoidal endothelial cells were all significantly hig her than those of the control group (t=3.771, P<0.05).Conclusions IP has a prot ective effect on liver function after hepatic resection with hepatic vascular e xclusion in HCC patients, possibly due to the inhibition of hepatocyte apoptosi s by down-regulating hepatic Fas mRNA expression and caspase-3 activity, and is a convenient technique applicable in such operations as hepatic transplants and hepatectomy.