Periostin (PN) is a kind of secreted glycoprotein, which is closely related to the metastatic potential and prognosis of many kinds of tumors in recent studies. However, the expression level of PN in hepatocellular carcinoma (HCC) and its correlation with tumor angiogenesis and prognosis remain unclear. Here Immunohistochemistry assay was used to determine the expression of PN in HCC and corresponding adjacent tissues from 71 patients. VEGF and CD34 were only examined in HCC tissues of patients mentioned above. Immunohistochemically, the expression of PN in HCC was judged to be positive in 73.2 % (52/71) compared with 19.7 % (14/71) in corresponding adjacent tissues, and it was associated with tumor nodules (P = 0.070), microvascular invasion (P = 0.013), Edmondson grade (P = 0.003), tumor capsula (P = 0.038) and TNM stage (P = 0.000); besides, tumors with PN-positive group expressed higher VEGF (82.7 vs. 26.3 %, χ (2) = 20.195, P = 0.000) and had higher MVD (80.5 ± 36.5 vs. 24.0 ± 19.9, t = -6.395, P = 0.000) than those in PN-negative group. Kaplan-Meier method was used for survival analysis, and Cox regression model was performed for multivariate survival analysis. In particular, the expression of PN was found to be an independent factor for predicting overall and disease-free survival of HCC. It is possible that the expression level of PN in HCC is associated with tumor metastatic potential and angiogenesis. Its abnormal expression could be a predictive factor to anticipate HCC patient's prognosis after surgery.