The cooperative role of CD4⁺ helper T (Th) cells has been reported for CD8⁺ cytotoxic T (Tc) cells in tumor eradication. However, its molecular mechanisms have not been well elucidated. We have recently demonstrated that CD4⁺ Th cells can acquire major histocompatibility complex/peptide I (pMHC I) complexes and costimulatory molecules by dendritic cell (DC) activation, and further stimulate naïve CD8⁺ T cell proliferation and activation. In this study, we used CD4⁺ Th1 and CD8⁺ Tc1 cells derived from ovalbumin (OVA)‐specific T cell receptor (TCR) transgenic OT II and OT I mice to study CD4⁺ Th1 cell's help effects on active CD8⁺ Tc1 cells and the molecular mechanisms involved in CD8⁺ Tc1‐cell immunotherapy of OVA‐expressing EG7 tumors. Our data showed that CD4⁺ Th1 cells with acquired pMHC I by OVA‐pulsed DC (DC_OVA) stimulation are capable of prolonging survival and reducing apoptosis formation of active CD8⁺ Tc1 cells in vitro, and promoting CD8⁺ Tc1 cell tumor localization and memory responses in vivo by 3‐folds. A combined adoptive T‐cell therapy of CD8⁺ Tc1 with CD4⁺ Th1 cells resulted in regression of well‐established EG7 tumors (5 mm in diameter) in all 10/10 mice. The CD4⁺ Th1’s help effect is mediated via the helper cytokine IL‐2 specifically targeted to CD8⁺ Tc1 cells in vivo by acquired pMHC I complexes. Taken together, these results will have important implications for designing adoptive T‐cell immunotherapy protocols in treatment of solid tumors.