The cancer cell membrane (CCM) is widely used for nanomedicine encapsulation to improve their tumor-targeting ability. However, few researches are focused on drug release process and mechanism of these composite. Cell membrane fusion (two separate lipid membranes merge into a single continuous bilayer), one of the most fundamental processes in biology could be promoted by heating. Thus, in this manuscript, CCM was exploited as the gate keeper and tumor-targeting moiety of anticancer drug-loaded mesoporous silica nanoparticles (MSN). In addition, the drug release process and mechanism based on cell membrane fusion were studied. The loaded drugs included indocyanine green (ICG), a FDA-approved near-infrared photothermal agent for clinical applications, and doxorubicin (DOX), a chemotherapy drug. By coating CCM on drug-loaded MSN, the keeper could prevent unexpected drug leaking during the circulation and provide tumor targeting based on its specific recognition function. After arriving tumor tissue post-tail vein injection, the tumor position is irradiated by 808nm light to trigger light-thermal conversion process of ICG to heat the composite (DOX-ICG@MSN@CCM) and promote cell membrane fusion between the encapsulated CCM and targeted tumor cell membrane. Such process can enhance the uptake efficacy of DOX-ICG@MSN@CCM to tumor cells. Furthermore, ICG could provide a synergistic photothermal therapy activity with DOX.