Hepatitis C virus (HCV) infects ≈2% of the world’s population. HCV infection not only causes acute and chronic hepatitis, but also leads to liver cirrhosis and hepatocellular carcinoma (HCC). The molecular pathogenesis of HCV infection has been explored and many evidence indicated that autophagy is an important process for its life cycle, although autophagy was thought as a mechanism to eliminate invaded HCV from hepatocyte. Structural and non-structural proteins of HCV are important regulators of autophagy, and HCV uses autophagy as a necessary step in its replication. Down-regulation of innate immune response by HCV through unfolded protein response (UPR) and autophagy induction was used as a pathway to establish chronic HCV infection in the liver. Meanwhile, the infected hepatocyte is also using autophagy mechanism to eradicate HCV virus from liver. The study on relationship between HCV and autophagy will pave the new way to understand HCV life cycle and to find new strategy for prevention and treatment of liver diseases caused by HCV infection.