Objective: To investigate the relation of caveolin-1 with invasion and metastasis of hepatocellular carcinoma (HCC) and possible underlying mechanism. Methods: The caveolin-1 mRNA expressions in the tumor tissues from HCC patients with intrahepatic metastasis and their adjacent tissues, as well as cirrhosis and normal liver tissues were detected by real-time PCR method. The caveolin-1 protein expressions in the tumor tissues from HCC patients with intrahepatic metastasis and their adjacent tissues were determined by Western blot analysis. Immunohistochemical staining was performed on the HCC specimens from 75 HCC cases to detect the expression of caveolin-1, vascular endothelial growth factor (VEGF), CD34 and α-smooth muscle actin (α-SMA), and then the relations of caveolin-1, VEGF, microvessel density (MVD) and unpaired artery (UA) with the clinicopathological factors of HCC patients were analyzed. Results: Of the HCC patients with intrahepatic metastasis, the expression level of caveolin-1 mRNA in tumor tissues was significantly higher than that in their adjacent tissues, cirrhosis and normal liver tissues (all P<0.05), and its protein expression in tumor tissues was significantly higher than that in their adjacent tissues. The increased expression of caveolin-1 in HCC was associated with metastasis (P<0.05), and caveolin-1 expression was positively correlated with VEGF expression, MVD and UA (r=0.293, P=0.011; r=0.361, P=0.001; r=0.388, P=0.001). Conclusion: Increased caveolin-1 expression may promote the invasion and metastasis of HCC and the possible mechanism is that it induces VEGF expression in HCC and thereby enhances tumor angiogenesis.