In this study, a sialic acid (SA) and transferrin (TF) imprinted biodegradable disulfide bridging organosilicas-based drug delivery system (SS-DMONS/DOX-Ce6@MIPs) for targeted cancer therapy was constructed, for the first time. Disulfide bridged dendritic mesoporous organosilicas nanoparticles (SS-DMONs) not only enhance drug loading as the drug repository, but also provide enough specific surface area for the molecular imprinting shell to expose more degradation and imprinted sites on the surface. In addition, -S-S- could be disturbed in a highly reducing tumor microenvironment to achieve degradation. The biodegradable imprinting film, prepared with customized 2-amino-N-(3,4-dihydroxyphenethyl)-3-mercaptopropanamide and 4-mercaptophenylboronic acid as functional monomers, endowed SS-DMONs with active targeting capacity, and responsive drug release through degradation under acidic and highly reductive tumor microenvironment. SS-DMONS/DOX-Ce6@MIPs after binding of TF could target tumor cells actively through multiple interactions, including the affinity between antigen and antibody, and the specific recognition between molecularly imprinted polymers and template molecules. Under laser irradiation the loaded chlorin e6 (Ce6) that can produce toxic reactive oxygen, combined with the doxorubicin (DOX), achieved chemical/photodynamic synergistic anticancer effects. SS-DMONS/DOX-Ce6@MIPs presented excellent tumor targeting and dual-responsive drug release, which provides an effective strategy for chemical/photodynamic anti-tumor therapy. This article is protected by copyright. All rights reserved.