The invention relates to a preparation method and an application of a pH-sensitive mixed micelle. An anti-cancer drug, namely DOX, is in covalent linkage with mPEG by virtue of acid-sensitive Cbm, an obtained material, as a polymer prodrug, is mixed with TPGS, and self-assembling is conducted in a water solution, so that the mixed micelle, which is of a core-shell structure, is formed. The pH-sensitive mixed micelle provided by the invention can, in response to a special low-pH environment of tumor tissues, can achieve specific release of the DOX, so that the excretion of the drug can be effectively inhibited and the multi-drug resistance of tumor cells can be reversed; and the mixed micelle is good in biocompatibility and long in drug circulating time, and the preparation method is convenient for operation and popularization and has a good development prospect.