Chemotherapy is an important first-line strategy for tumor therapy in cancer treatment, but multidrug resistance (MDR) is a major problem that reduces the efficacy of chemotherapeutics. Herein, we report a novel photothermally controlled intelligent drug release system (AuNP@mSiO-DOX-FA) with a large amount of drugs loading for synergistic chemo-photothermal therapy of MDR in breast cancer. The nanoplatform utilized gold nanoparticles as a hyperthermia core, and large-mesoporous silica as a shell for doxorubicin (DOX) loading. Benefiting from the thick layer and large pore size, the encapsulation and loading efficiency were as high as 97.7% and 8.84%, respectively. Furthermore, under the trigger of 808 nm near infrared (NIR) light, the released DOX increased significantly at pH 5.0 and reached to 39.0% in 20 min, achieving a facile intelligent control of chemotherapy additional to the photothermal therapy. The viability of MCF-7/ADR cells could be efficiently reduced to 16.9%, demonstrating the proposed photothermally controlled system with synergistic chemo-photothermal therapy has great potential capability to overcome MDR in breast cancer.