Compositions and methods are provided relating to human anti-HCV E2 monoclonal antibodies. The antibodies of the invention bind to a conserved region of HCV E2 protein, and neutralize HCV influenza virus across multiple HCV genotypes. Embodiments of the invention include isolated antibodies and derivatives and fragments thereof, pharmaceutical formulations comprising one or more of the human anti-HCV monoclonal antibodies and cell lines that produce these monoclonal antibodies.