Recently, nanoparticles that possess combined use in synergistic therapy, real-time imaging, and spatiotemporally controlled therapies have attracted enormous attention. Herein, we fabricated Doxorubicin (DOX)-loaded and beta-cyclodextrin (beta-CD)-capped mesoporous platinum nanoparticles (MPNPs) (DOX/MPNPs-AD-CD) for combined chemo-photothermal cancer therapy. DOX/MPNPs-AD-CD with high photothermal effect and loading rate could release the anticancer drugs stimulated by acidic tumor microenvironment or near-infrared light. Moreover, acid-degradable MPNPs would release cytotoxic Pt2+, which would enhance the efficiency of chemotherapy. In addition, the inherent photoacoustic and photothermal imaging can effectively guide chemo-photothermal therapy to achieve the desired treatment. Taken together, DOX/MPNPs-AD-CD possess the abilities of combined chemo-photothermal therapy and dual-imaging properties. The studies demonstrated that DOX/MPNPs-AD-CD could effectively inhibit tumor cell growth in vivo and in vitro. Thus, this treatment platform is expected to be one of interest for the clinical treatment of cancers.