Temozolomide prodrug nano-micelles each comprise a hydrophilic shell and a hydrophobic core; each hydrophilic shell is polyoxazoline or polyethylene glycol, and the hydrophobic cores are each polytemozolomide. A preparation method for the temozolomide prodrug nano-micelles is characterized in that the polyoxazoline or polyethylene glycol reacts with 4-cyano-4-valeric acid through an esterificationreaction, and as a macromolecular reversible addition-fragmentation chain transfer polymerization (RAFT) reagent, an obtained product reacts with temozolomide-methyl methacrylate under catalysis of azodiisobutyronitrile to obtain amphiphilic block polymers. According to the temozolomide prodrug nano-micelles, the amphiphilic block polymers can extend the half-life period of temozolomide; two amphiphilic block polymer nano-micelles both belong to the prodrugs of the temozolomide, and meanwhile, the cores of the micelles can entrap other anticancer drugs to realize combination therapy of different drugs. After entering a tumor cell, the polyoxazoline-polytemozolomide micelles crack in the acidic environment of the cancer cell, and encapsulated drugs are quickly released, and thereby, a high-efficiency therapeutic effect is generated, and the problems that a drug carrier is slow in drug release, and is prone to be drug-resistant are solved.