This study reports a smart controlled drug release system based on mesoporous silica nanoparticles (MSNs) for targeted drug delivery. The system was fabricated by employing heparin as an end-capping agent to seal the mesopores of MSNs via disulfide bonds as intermediate linkers for intracellular glutathione triggered drug release. Lactobionic acid molecules were then coupled to heparin end-capped MSNs that serve as targeting motifs for facilitating the uptake of doxorubicin (DOX) loaded MSNs by HepG2 cells and tumors, respectively. Detailed investigations demonstrated that the fabricated drug delivery systems could deliver DOX to cancer cells to induce cell apoptosis in vitro and tumor tissue for the inhibition of tumor growth in vivo with minimal side effects. The study affords a promising nanocarrier for redox-responsive cargo delivery with high curative efficiency for cancer therapy.