The marked disruption of CLDN1 and OCLN localization that we observed in both hepatoma cells and primary human hepatocytes upon TACSTD2 gene silencing recapitulates the in vivo observations and strongly suggests that downregulation of TACSTD2 in the tumor of HCV-infected HCC patients may be responsible for the altered localization and function of these two HCV-entry cofactors within malignant hepatocytes. Here, CLDN1 is linked to hepatocellular carcinoma.