Chimeric antigen receptor (CAR)-T cell therapy is a promising therapeutic approach in treating hematological malignancies. However, due to escape of CAR antigens in cancer cells, resistance and relapse occur in some patients after CAR-T cell therapy. Therefore, we investigated whether the combination with an antagonist of inhibitor of apoptosis proteins (IAP), tolinapant, currently being evaluated in a phase 2 study of peripheral T-cell lymphoma and cutaneous T-cell lymphoma, could enhance anti-tumor effect of CAR-T cell therapy. We found that tolinapant enhanced the antitumor effect of CAR-T cell therapy in a TNF-α-dependent manner. TNF-α secreted from CAR-T cells in the presence of tolinapant also induced cell death of antigen-negative cancer cells not in cell-cell contact with CAR-T cells. The significant combined effect was also observed in vivo. Even at ineffective doses of CAR-T cell monotherapy, anti-tumor effect was observed when the combination treatment was used. We propose that this is because tolinapant induced both cancer cell death and CAR-T cell proliferation. In summary, we find that combination therapy with tolinapant improved the efficacy of CAR-T cells by inducing cancer cell death and CAR-T cell proliferation. This combination therapy may overcome the current limitations of CAR-T cell therapy.