Hepatitis C virus cell entry is mediated by multiple factors, including various receptors and cellular factors that trigger virus uptake by the hepatocyte. Occludin is a newly identified essential co-receptor for HCV entry together with CD81, SR-B1 and CLDN1. CLDN1 and occludin highlight the importance of studying the effects of tight junction and cell polarization on HCV entry. Study on cell polarization and tight junction can help to discover new targets for HCV therapy, and therefore interfere the cell entry and cell-cell spread of HCV. This review summarizes the current knowledge of hepatocyte polarization, tight junction and its major integral proteins CLDN1 and occludin, polarized cell culture system and its relation with HCV entry. \[Key words\] hepatitis C virus; cell polarization; tight junction; cell entry; occludin