Drug-loaded micelles with long circulation time in blood and stimuli-responsiveness under the tumor micro-environment can significantly enhance therapeutic efficacy. In this report, human hair keratin was extracted with a reduction method and then conjugated with zwitterionic poly(2-methacryloxyethyl phosphatidylcholine, MPC) via thiol chain transfer polymerization (thiol CTP). Subsequently, keratin-polyMPC conjugates (KPC) were prepared into micelles and loaded with doxorubicin (DOX) by self-assembly. These micelles exhibited pH, glutathione (GSH), and enzyme triple-responsiveness as well as charge reversibility under the tumor micro-environment. In addition, these micelles showed high toxicity against A549 cells while low toxicity to normal cells. In vivo anticancer efficacy results revealed that these micelles showed better therapeutic efficiency than free DOX. Furthermore, these carriers exhibited prolonged circulation time, good stability, and no hemolysis in blood. Based on the results, these drug delivery systems of micelles were proper candidates as drug carriers.