Indications for resection of hepatocellular carcinoma (HCC) remain controversial. This study aimed to identify prognostic factors that affect overall survival (OS) and disease-free survival (DFS) in patients with HCC after hepatectomy. From 2004 to 2010, 601 patients with HCC who underwent resection were enrolled. Factors stratified into the host, biochemical, surgical treatment and tumor-related features in terms of recurrence and overall survival were analyzed. Prognostic factors were evaluated by univariate and multivariate analyses, with Kaplan-Meier survival analyses and Cox proportional hazard model. The overall survival rates of 1-, 3- and 5- year were 79, 62, and 54 %, and the corresponding DFS rates were 51, 38 and 31 %, respectively. In a multivariate analysis, Child-Pugh, serum AFP level, ALT level, time for hepatic resection, tumor differentiation, maximum size of tumors, local necrosis, portal vein tumor thrombus, and TNM Stage were correlated significantly with patients' OS. Gender (P = 0.046), cigarette smoking (P = 0.007), serum AFP level (P = 0.001), GGT level (P = 0.002), maximum size of tumors (P = 0.009), liver cirrhosis (P = 0.025), portal vein tumor thrombus (P = 0.022), microvascular tumor thrombus (P = 0.007) and TNM Stage (P = 0.001) were significantly affected DFS. Preoperative AFP level, maximum size of tumors, portal vein tumor thrombus and TNM Stage were revealed as important prognostic factors for OS and DFS through follow-up of a relatively large cohort of Chinese HCC patients.