Abstract: Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer globally. Indeed, only few treatments are available, most of which are effective only for the early stages of the disease. Therefore, there is an urgent needing of potential markers for a specifically targeted therapy. Candidate proteins were selected from datasets of The Human Protein Atlas, in order to identify specific tumor-associated proteins overexpressed in HCC samples associated with poor prognosis. Potential epitopes were predicted from such proteins and homology with peptides derived from viral proteins was assessed. A multiparametric validation was performed, including recognition by PBMCs from HCC-patients and healthy donors, showing a T cell cross-reactivity with paired epitopes. These results provide novel HCC-specific Tumor-associated antigens (TAAs)TAAs for immunotherapeutic anti-HCC strategies potentially able to expand pre-existing virus-specific CD8+ T cells with superior anti-cancer efficacy.