Increasing evidence has shown that hepatectomy provides a longer overall survival (OS) for patients with hepatocellular carcinoma (HCC) in the intermediate stage. Unfortunately, not all patients benefit from liver resection, even if hepatectomy is feasible. This study aimed to propose a subclassification to select patients for surgical resection.OS of patients with intermediate-stage HCC who underwent hepatectomy at Beijing Friendship Hospital or Peking Union Medical College Hospital were reviewed. Patients were divided into 2 groups based on the results of survival analysis. The prognosis of these patients was compared with that in those who were treated by trans-arterial chemoembolization (TACE) in each subgroup.A total of 259 patients with intermediate-stage HCC who were initially treated by hepatectomy were included. Multivariate analysis showed that cumulative tumor size and tumor number independently affected tumor recurrence and survival time of these patients. Patients were then divided into group A (tumor size <11cm and tumor number < 4; n=205) and group B (tumor size 11cm and tumor number 4; n=54). Multivariate analysis showed that hepatectomy was independently associated with longer OS compared with TACE in patients in group A (hazard ratio=0.67, 95% confidence interval=0.49-0.90), but not in group B.Surgical management of intermediate-stage HCC should be performed with more complexity than current practice. Hepatic resection could be considered as the first-line treatment only for patients with HCC who have a cumulative tumor size of less than 11cm and <4 tumors.