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The purpose of the study is to evaluate the protective effects of Verapamil on hepatic ischemia–reperfusion injury in cirrhotic patients with HCC. A controlled study was performed on 86 consecutive patients with cirrhosis who underwent liver resection for suffering HCC. Thirty-nine patients were injected with Verapamil through the mesenteric vein before Pringle's maneuver to alleviate hepatic ischemia–reperfusion injury, while 47 patients were not. The serum AST, ALT, and total bilirubin on days 1 and 3 were markedly lower in the Verapamil group than that in the control group postoperatively (AST, P < 0.001 and P < 0.001; ALT, P < 0.001 and P = 0.042; TB, P = 0.037 and 0.049; respectively). The serum hyluronic acid on day 1 was also significantly lower in Verapamil group than that in the control group ( P < 0.01), but no marked difference on days 3 and 7. Meanwhile, the levels of IL6 on days 1 and 3 were markedly lower in the Verapamil group than that in control group ( P < 0.05 and P < 0.01, respectively. The new Clavien's classification of surgical complications showed marked severity in the control group than that in the Verapamil group ( P = 0.021), especially in the grade I level ( P = 0.045). Verapamil may serve as protective agent for hepatic ischemia–reperfusion injury in cirrhotic patients with HCC. Therefore, Verapamil can be used for treatment of patients who are to undergo hepatectomy with occlusion of hepatic blood flow. [ABSTRACT FROM AUTHOR]