Silencing ofOPN expression by OPN siRNA and immunodepletion of OPN by anti-OPN antibody resultedin reduced EMT, migration, and invasion of human hepatocytes, which may be a usefultarget in developing a better therapeutic strategy for liver cancer associated withchronic hepatitis C. Our results also provide novel insight into the mechanisms ofHCV-infected hepatocytes migration and HCC. This evidence concerns the gene SPP1 and hepatitis C virus infection.