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Biodegradable micelles with sheddable poly(ethylene glycol) shells were developed based on disulfide-linked poly(ethylene glycol)-b-poly(epsilon-caprolactone) (PEG-SS-PCL) diblock copolymer and applied for rapid intracellular release of doxorubicin (DOX). PEG-SS-PCL was prepared with controlled block lengths via exchange reaction between PEG orthopyridyl disulfide and mercapto PCL. The micelles formed from PEG-SS-PCL, though sufficiently stable in water, were prone to fast aggregation in the presence of 10mm dithiothreitol (DTT), due to shedding of the PEG shells through reductive cleavage of the intermediate disulfide bonds. Interestingly, the in vitro release studies revealed that these shell-sheddable micelles released DOX quantitatively within 12h under a reductive environment analogous to that of the intracellular compartments such as cytosol and the cell nucleus. In contrast, minimal drug release (<20%) was observed within 24h for the reduction insensitive PEG-PCL micelles under the same conditions as well as for PEG-SS-PCL micelles under the non-reductive conditions. Remarkably, cell experiments showed that these shell-sheddable micelles accomplished much faster release of DOX inside cells and higher anticancer efficacy as compared to the reduction insensitive control. These shell-sheddable biodegradable micelles are highly promising for the efficient intracellular delivery of various lipophilic anticancer drugs to achieve improved cancer therapy.