An enzyme-responsive drug delivery system was constructed from a pillar[5]arene-based polyethyleneglycol-substituted amphiphile which self-assembles into micelles in water. These micelles exhibit superior drug encapsulation capability, and display drug release behaviour in response to enzyme catalysis, in partiular to L-asparaginase. Doxorubicin-loaded micelles show significant cytotoxicity against MCF-7 cancer cells.