Background. Nearly 20% of human cancers worldwide have an infectious etiology with the most prominent examples beinghepatitis B and C virus-associated hepatocellular carcinoma and human papilloma virus-associated cervical cancer. There is anurgent need to find new approaches to treatment and prevention of virus-associated cancers. Methodology/PrincipalFindings. Viral antigens have not been previously considered as targets for treatment or prevention of virus-associatedcancers. We hypothesized that it was possible to treat experimental HPV16-associated cervical cancer (CC) and Hepatitis Bassociatedhepatocellular carcinoma (HCC) by targeting viral antigens expressed on cancer cells with radiolabeled antibodiesto viral antigens. Treatment of experimental CC and HCC tumors with 188Re-labeled mAbs to E6 and HBx viral proteins,respectively, resulted in significant and dose-dependent retardation of tumor growth in comparison with untreated mice ormice treated with unlabeled antibodies. Conclusions/Significance. This strategy is fundamentally different from the prioruses of radioimmunotherapy in oncology, which targeted tumor-associated human antigens and promises increased specificityand minimal toxicity of treatment. It also raises an exciting possibility to prevent virus-associated cancers in chronicallyinfected patients by eliminating cells infected with oncogenic viruses before they transform into cancer.