Focal adhesion kinase plays a critical role in cancer progression, invasion, and metastasis. Although focal adhesion kinase overexpression indicates poor prognoses for hepatocellular carcinoma, its role in hepatocellular carcinoma metastasis has not been well investigated. In this study, 55 hepatocellular carcinoma patients were enrolled, and their primary liver tumors as well as 18 matched metastases were subjected to semiquantitative immunohistochemistry analysis of focal adhesion kinase expression. Overexpression of focal adhesion kinase was observed in 34 (61.8%) of 55 primary tumors and significantly predicted subsequent extrahepatic metastases (P = .04). Metastatic tumors expressed higher focal adhesion kinase than their matched primaries (P = .010). Focal adhesion kinase overexpression indicated both worse overall 5-year survival rate (51.5% ? 8.7% versus 90.2% ? 6.6%; P = .004) and 5-year progression-free survival rate (51.5% ? 8.7% versus 90.2% ? 6.6%; P = .041). Taken together, we demonstrated here that focal adhesion kinase expression is significantly related to subsequent hepatocellular carcinoma metastasis. Focal adhesion kinase is thus considered as a reasonable target for novel therapies against hepatocellular carcinoma progression and metastasis.