Cancer is one of the major causes of human death. There are many types of cancer treatment including surgery, chemotherapy, radiotherapy, and photothermal therapy. Combining different therapies can synergistically enhance the therapeutic effect. We developed porous hollow palladium nanoparticles (PHPdNPs) to co-deliver ¹³¹I (a radioisotope that is commonly used in radiotherapy) and doxorubicin (DOX; a chemotherapy drug). Compared with other mesoporous nanocarriers, our PHPdNPs exhibited impressive photothermal conversion efficiency and stability. Drug loading is high and drug release is controllable by repeated laser irradiation and acidic pH in tumor microenvironments. Owing to the specific interaction between palladium and iodine, the PHPdNPs serve as effective ¹³¹I delivery vehicles with excellent radiochemical stability. A single dose of [¹³¹I]PHPdNPs-DOX has superior antitumor efficacy because it enables a combination of chemo-, photothermal-, and radio-therapy. Moreover, the nanocomplex has no obvious side-effects in mice. Therefore, we believe that PHPdNPs are excellent candidates for multimodal imaging-guided therapy.