Oral chemotherapy is the preferred route for cancer treatment because it can improve the efficacy and decrease the side effects. Unfortunately, most anticancer drugs suffered from their poor oral bioavailability. Herein, we construct a novel pH-triggered oral drug delivery system by capping of mesoporous silica SBA-15 with pH-responsive polymer poly (acrylic acid) (PAA) via a facile graft-onto strategy. The experiment results demonstrated that the PAA brushes were anchored on the pore outlets of mesoporous silica SBA-15, which can be acted as the gatekeeper to control the drug molecules transport in and out of the pore channels. The PAA capped mesoporous SBA-15 (PAA/SBA-15) exhibited a high drug loading capacity (785.7mg/g), excellent pH-sensitivity and good biocompatibility. In gastric environment (pH=2.0), the drug doxorubicin (DOX) molecules were encapsulated in the pore channels because the pore outlets were capped with collapsed PAA. In contrast, in colonic environment (pH=7.6), it exhibited a fast release because of the removal of capping. In addition, the water solubility of DOX in colonic environment was enhanced after DOX being loaded into the pores of PAA/SBA-15. This pH-triggered oral drug delivery system has promising applications for treatment of colon cancer and other colon diseases.