As a drug delivery system (DDS), traditional mesoporous silica nanoparticles (MSNs) suffer from bioaccumulation in vivo and premature drug release in systemic circulation due to low degradation rate and lack of protective gatekeeper. Herein, we developed a safe and intelligent DDS with characteristics of pH-responsive biodegradation and controlled drug release based on mesoporous silica composite nanoparticles (MSCNs) capped with ZnO quantum dots (ZnO QDs). Acidic degradable MSCNs were successfully synthesized by doping Ca and PO into the MSNs' framework. The in vitro doxorubicin hydrochloride (DOX) release was inhibited at neutral pH 7.4 but triggered significantly at pH 5.0 due to the dissociation of ZnO caps. The internalization behavior and cytotoxicity of 4T1 cells indicated MSCNs-ZnO could efficiently deliver DOX into the cells with significant antitumor activity. Such a DDS with pH-responsive biodegradation and controlled drug release has promising potential for cancer therapy.