Hepatocellular carcinoma (HCC) is the second leading cause of cancer death in China. We aimed to first present the expression of endocan in HCC tissue and its correlation with the clinicopathological features and overall survival of patients with HCC after curative hepatectomy. Immunohistochemical detection of endocan, CD34, and vascular endothelial growth factor (VEGF) were performed on samples from 100 patients with HCC. Endocan protein was expressed in endothelium of HCC tissue in all specimens, but was not expressed in endothelium of pericarcinomatous liver tissue and normal liver tissue. Microvessel density (MVD) denoted by endocan (endocan-MVD) in HCC was correlated with microscopic venous invasion and VEGF expression (P < 0.05). Survival analysis showed that overall survival of patients was inversely associated with endocan-MVD (P < 0.01). Multivariate analysis showed that endocan-MVD was an independent prognostic marker for overall survival of HCC (P < 0.01). In conclusion, endocan-MVD was a significant factor to predict the prognosis of HCC patients after curative hepatectomy.