Intelligent drug delivery systems have attracted great attention in the field of biomedicine and cancer diagnosis. In this work, a drug delivery system that can be gated by doxorubicin itself and together with pH-responsive ability has been designed and prepared based on the upconversion nanoparticles. The drug delivery system is a special core-shell structure, consisting of upconversion nanoparticle core and mesoporous silica shell. The new system tactfully bypasses the use of auxiliary capping agents and exhibits desirable drug release at pH = 5, enhancing HeLa cells inhibition. The introduction of Schiff base plays a key role in the process of achieving pH-responsive drug release. Moreover, upconversion nanoparticles could emit bright yellow-green fluorescence (540 nm) under the irradiation of near-infrared light (980 nm) for in vivo bioimaging. This characteristic provides the possibility of locating tumor tissues and real-time tracing drug delivery.