Metastasis/recurrence has been the most fundamental characteristic of hepatocellular cancer (HCC) and the ultimate cause of most HCC-related deaths. However, there are still a limited number of reliable tumor markers that can be used to predict the possibility of metastasis/recurrence in an HCC patient after operation. Recently, much evidence has shown that glypican-3 (GPC3) can be a useful tool to identify the early development of HCC, but little research has been done to test its usefulness as a prognostic marker related to post-operative metastasis/recurrence in HCC patients. In this study, the expression of GPC3 and its relationship with clinicopathological factors were determined by immunohistochemical analysis in 61 primary HCC patients. The potential prognostic value of GPC3 was investigated by comparing the survival time between HCC patients with high and low GPC3 expression. The results demonstrated that GPC3 expression was closely related with metastasis/recurrence in an HCC patient who can receive the operation. The risk of metastasis/recurrence after surgery in an HCC patient with high GPC3 expression was increased to 3.214 as compared to that of an HCC patient with low GPC3 expression. Survival analysis showed that HCC patients with high GPC3 expression had a significantly shorter overall survival time than HCC patients with low GPC3 expression (P=0.003). Further, multivariate analysis showed that GPC3 expression was a significant, independent prognostic parameter (P=0.030) for HCC patients. Overall, the study indicates that GPC3 might be a valuable marker closely related with prognosis and post-operative metastasis/recurrence in HCC patients.