The combination of chemotherapy and photothermal therapy (PTT) into a single formulation has attracted increasing attention as a strategy for enhancing cancer treatment. Here, hollow mesoporous silica nanoparticles (HMSNs) were used as a base carrier material, loaded with the anti-cancer drug doxorubicin (DOX), and surface functionalized with chitosan (CS) and copper sulfide (CuS) nanodots to give HMSNs-CS-DOX@CuS. In this formulation, the CuS dots act as gatekeepers to seal the surface pores of the HMSNs, preventing a burst release of DOX into the systemic circulation. S-S bonds connect the CuS dots to the HMSNs; these are selectively cleaved under the reducing microenvironment of the tumor, permitting targeted drug release. This, coupled with the PTT properties of CuS, results in a potent chemo/PTT platform. The HMSNs-CS-DOX@CuS nanoparticles have a uniform size (150 ± 13 nm), potent photothermal properties (η= 36.4 %), and tumor-targeted and near infrared (NIR) laser irradiation-triggered DOX release. In vitro and in vivo experimental results confirmed that the material has good biocompatibility, but is effectively taken up by cancer cells. Moreover, the CuS nanodots permit, simultaneous thermal/photoacoustic dual-modality imaging. Treatment with HMSNs-CS-DOX@CuS and NIR irradiation caused extensive apoptosis in cancer cells both in vitro and in vivo, and could dramatically extend the lifetimes of animals in a murine breast cancer model. The system developed in this work therefore merits further investigation as a potential nanotheranostic platform for cancer treatment. STATEMENT OF SIGNIFICANCE: : Conventional cancer chemotherapy is accompanied by unavoidable off-target toxicity. Combination therapies, which can ameliorate these issues, are attracting significant attention. Here, the anticancer drug doxorubicin (DOX) was encapsulated in the central cavity of chitosan (CS)-modified hollow mesoporous silica nanoparticles (HMSNs). The prepared system can target drug release to the tumor microenvironment. When exposed to near infrared laser (NIR) irradiation, CuS nanodots located at the surface pores of the HMSNs generate energy, accelerating drug release. In addition, a systematic in vitro and in vivo evaluation confirmed the HMSNs-CS-DOX@CuS platform to give highly effective synergistic chemotherapeutic-photothermal therapy and have effective thermal/photoacoustic dual-imaging properties. This work may open up a new avenue for NIR-enhanced synergistic therapy with simultaneous thermal/photoacoustic dual imaging. Copyright © 2021. Published by Elsevier Ltd.