Fe3O4@mSiO2 (magnetic Fe3O4 core coated by a mesoporous silica shell) nanoparticles were successfully synthesized as a carrier. The anti-cancer drug doxorubicin (DOX) and chlorambucil (Chl) were used as the model cargo. After the drug-loading, a sodium hyaluronic acid (HA) cross-linked gel was adopted to coat the outside of the Fe3O4@mSiO2 nanoparticles as a layer (named as drug–Fe3O4@mSiO2–HA) to prevent drug pervasion. The detailed release kinetics were investigated, revealing the sensitive release triggered by hyaluronidase (HAase), a major enzyme which is rich in the tumor microenvironment, which can degrade the HA shell to induce the enzyme sensitive drug release. Moreover, there are some HA receptors in many tumor areas, associating with magnetic targets to further ensure the specific targeted drug delivery. With these improved performances, these smart multifunctional nanocomposites are expected to possess potential applications in the biopharmaceutical for cancer therapy.