Up to now, little is known about hepatitis B virus core protein (HBc) interactions with host-cell proteins, although such interactions might be essential for virus propagation and pathogenicity. In this work, a human liver cDNA library was screened for proteins interacting with HBc. Among several HBc-interacting partners selected, it interacted most strongly with the human protein GIPC1. A common protein interaction domain, PDZ, was identified as the region that is sufficient for the interaction with HBc. The core protein has a putative C-terminal PDZ-interacting motif, and this sequence proved to be important for the interaction with GIPC1.