A novel intelligent active defense system that can specially respond to cancerous tissues for drug release was designed and prepared. The active defense system consists of a biodegradable dextran microgel core cross-linked by a Schiff's base and a surrounding layer formed by Layer-by-Layer (LbL) assembly. The loading and release of macromolecular model drug, dex-FITC, as well as antineoplastic drug, DOX, was investigated. The in vitro cell inhibition and drug release behavior of the drug delivery system were studied and the results showed that the entrapped drug could be explosively released from the microcapsules and thereafter taken up by cancer cells upon the trigger of the acidic environment around tumor tissues.