The preparation of pH-labile polymer-drug particles via mesoporous silica-templated assembly for anticancer drug delivery into cancer cells is reported. The polymer-drug conjugate is synthesized via thiol-maleimide click chemistry using thiolated poly(methacrylic acid) (PMASH) and a pH-labile doxorubicin (Dox) derivative. Drug-loaded polymer particles that are stable under physiological conditions are obtained through infiltration of the conjugates into mesoporous silica particles, followed by cross-linking the PMASH chains, and subsequent removal of the porous silica templates. The encapsulated Dox is released from the particles through cleavage of the hydrazone bonds between Dox and PMASH at endosomal/lysosomal pH. Cell viability assays show that the assembled PMASH particles have negligible cytotoxicity to LIM1899 human colorectal cancer cells. In comparison, Dox-loaded PMASH particles cause significant cell death following internalization. The reported particles represent a novel and versatile class of stimuli-responsive carriers for controlled drug delivery.