Recently, hollow structures have attracted much attention due to their high specific surface area, clear interior space, low density and good permeability. Among them, manganese dioxide (MnO2) hollow structure has also been widely studied for catalysis, drug delivery and energy storage. Based on the characteristics of low pH and high GSH concentration in tumor microenvironment, it is possible to develop an intelligent drug delivery system with pH/GSH response based on hollow mesoporous MnO2 nanospheres. In addition, the excellent physical and chemical properties of MnO2 nanomaterials provide conditions for its synergistic photothermal therapy. For example, Mn2+ released after manganese dioxide reacts with GSH can enhance T1-MAGNETIC resonance (MR) imaging. Meanwhile, manganese dioxide can also react with H2O2 in tumor microenvironment to release oxygen and alleviate tumor hypoxia. In order to prevent drug loss during delivery, a GSH-responsive hollow mesoporous manganese dioxide microsphere was selected as the drug carrier in this paper, and a series of studies were carried out on the performance of the carrier. Hollow mesoporous MnO2 nanospheres with particle size below 100 nm were prepared by hydrothermal method, and their response to tumor microenvironment was simulated in vitro. It has been proved that hollow mesoporous MnO2 nanospheres can be desorbed at low pH and GSH response, and can be used to deliver drugs or photothermal agents, as well as for collaborative cancer imaging and treatment.