Objective: To investigate the safety and efficacy of surgical treatment in hepatocellular carcinoma (HCC) combined with moderate/severe portal hypertension (PHT). Methods: From January 2005 to December 2011, 247 patients with HCC-PHT who met the criteria were designated to undergo simple hepatectomy (none, mild or moderate PHT) or undergo hepatectomy plus azygos-portal disconnection. The laboratory parameters and postoperative risk factors such as hepatic encephalopathy, ascites, gastric ulcer and recurrent bleeding between the two groups were compared and analyzed. Results: Compared with the simple hepatectomy group, the postoperative liver function recovery and the incidence of hepatic encephalopathy, ascites, gastric ulcer and recurrent bleeding in the combination surgery group showed no significant difference (all P>0.05), but the postoperative white blood cell (WBC) and platelet counts significantly increased, and the long-term risk of recurrent bleeding significantly decreased in the combination surgery group (all P<0.05). Conclusion: The synchronous operation is a safe and effective method for treatment of HCC with severe PHT. It can improve the quality of life in this subset of patients but does not increase the surgical mortality and postoperative complications.