As classical therapy method of advanced hepatocellular carcinoma (HCC) is not effective enough, HCC immunotherapy is a hot spot for research in recent years. Although in recent years, immune checkpoint inhibitors are focused in cancer therapy, vaccines and adoptive cell therapy (ACT), as traditional immunotherapy methods for HCC are still promising. We found that δ-Catenin might be a new tumor-associated antigen for HCC, for it could be upregulated as a stress associated protein under hypoxia and irradiation treatment. δ-Catenin peptide vaccines could inhibit the growth of subcutaneous hepatocellular tumors in vivo. According to our work, δ-Catenin peptide vaccines could stimulate the activation of cytotoxic T lymphocytes (CTLs) and enhance the infiltration of CD8+ T cells into tumors. Moreover, δ-Catenin peptide vaccines could enhance the secretion of IFN-γ and the killing of tumor cells by T cells. Mechanistically, δ-Catenin peptide vaccines, presented by antigen-presenting cells to T cells, could enhance the activation of T cells via MAPK/ERK signaling and the transcriptional factors Eomes and T-bet. Our research results indicate new potential peptide vaccines, which can be applied in clinical HCC therapy.