Abstract: Smart drug carrier can precisely deliver drugs to the disease sites, improving the drug efficacy and reducing the side effects. In this paper, MSNs@polymer (FITC/FA) were prepared through grafting pH-sensitivepoly(2-(Diisopropyl amino) ethyl methacrylate) (PDPA), polyethylene glycol (PEG) and folic acid/fluorescence (FA/FITC) onto the surface of mesoporous silica(MSNs) using atom transfer radical polymerization (ATRP) and click chemistry. The system was developed by using the polymer as an end-capping group to seal the mesopores of MSNs, which is used for intracellular acid triggered drug release. A series of characterization techniques were applied to characterize and confirm the structures of the intermediates and the core-shell structured nanoparticles (MSNs@polymer(FITC/FA)) composing of inorganic and organic composite. The cell experiments including flow cytometry analysis, confocal laser scanning microscopy observations and cytotoxicity studies suggested that the nanocarriers were efficiently endocytosed by HeLa cancer cells, indicating the good biocompatibility of the nanoparticles, and their targeting and traceability for tumor cells. The nanoparticles could load both the antitumor drugs of paclitaxel (PTX) and tacrolimus (FK506) in the core and shell layers, respectively. PTX and FK506 were easily encapsulated into the nanocarriers with a high loading capacity, and were quickly released in response to the stimuli of acid. The drugs leakage was only about 20% under neutral condition (pH 7.4), but reached more than 80% at pH 5.0 after 24 h. Furthermore, it was proved that the two drugs could be released successively when the drugs were loaded into the core and shell, respectively. MSNs@polymer(FITC/FA) are expected to solve the problem of multi-drug resistance of antitumor drugs in clinic.