There is disclosed compositions and methods relating to or derived from anti-CD147 antibodies. More specifically, there is disclosed fully human antibodies that bind CD147, CD147-binding fragments and derivatives of such antibodies, and CD147-binding polypeptides comprising such fragments. Further still, there is disclosed nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating or diagnosing subjects having CD147 related disorders or conditions. There is also disclosed a method for treating CD147-expressing tumors, including hepatocellular carcinomas and squamous carcinomas, and non-oncology diseases selected from the group consisting of rheumatoid arthritis, experimental lung injury, atherosclerosis, chronic liver disease induced by hepatitis C vims, ischemic myocardial injury and heart failure.