The various immunological roles of human alpha-fetoprotein (HAFP), and its correlation with hepatomas, that is, hepatocellular carcinomas (HCCs), are not often addressed together in biomedical reports considering that HAFP is an established biomarker for hepatomas. Studies reporting measurement of HAFP serum levels in hepatoma patients in basic/clinical research settings has greatly increased over the years. Recent reports have now expanded our base knowledge in the mounting of an immune response against AFP, a self antigen, during hepatoma tumorigenesis. Advances in the detection and identification of AFP-derived peptide epitopes are opening new vistas of knowledge regarding the immunological role of AFP-peptides as T cell stimulating antigens in the course of hepatoma growth and progression. The present commentary addresses HAFP-derived peptides as immunologic responders in HCC and their use in the study and generation of AFP-peptide sensitized T cells directed against hepatoma cells. Attempts were further made to relate the AFP-derived peptide epitopes to T cell activities during the course of hepatoma immunotherapies and to profile the traits and properties of the peptides themselves. Hence, the present commentary was divided into two sections; (1) the characterization, properties, and traits of AFP peptide epitopes, and (2) the use of AFP-derived peptides in the therapeutic induction of T cells primed against hepatoma cells using both in vivo and in vitro models.