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The accurate treatment of tumors with the help of multimodality imaging is of great significance. Herein, a novel multifunctional probe combining active targeted fluorescent imaging (FL)/photoacoustic imaging (PA) and chemo-photothermal therapy for tumors has been designed. Targeting molecule folate (FA) modified graphene oxide (GO) was used to coat core–shell silver sulfide@mesoporous silica (QD@Si) while antitumoral doxorubicin (DOX) was loaded in mesoporous channels by electrostatic adhesion, and a delivery system (QD@Si-D/GO–FA) for active targeted dual-mode imaging and synergistic chemo-photothermal for tumors was successfully obtained. Experiments showed the cell survival rate was 76.3 ± 4.6% when the probe concentration reached 0.5 mg mL−1, and demonstrated that the probe had good biocompatibility. In vivo and in vitro results indicated that this probe could be used for active targeted FL/PA for tumors with overexpressed FA receptors. The temperature of the tumor rose to 63.5 °C under laser irradiation, and the tumor could be killed more effectively after combination with chemotherapy, which was caused by exfoliation of GO from QD@Si-D/GO–FA after irradiation. These results showed that the probe had great potential for application in oncology and is expected to provide evidence for early diagnosis and treatment of tumors. [ABSTRACT FROM AUTHOR]