In this study we used overlapping peptides spanning the entire sequences of AFP, GPC‐3, MAGE‐A1, and NY‐ESO‐1 in a cohort of 96 HCC patients to evaluate naturally occurring CD8+ T‐cell responses against four major HCC‐associated TAA irrespective of HLA restriction. The gene discussed is GPC3; the disease is hepatocellular carcinoma.