The invention discloses a preparation method and application of degradable hyperbranched polyamidoamine. Degradable hyperbranched polyamidoamine is prepared by taking a bifunctional monomer containing a disulfide bond or a ketal bond and an amino-containing trifunctional monomer N-aminoethylpiperazine (AEPZ) or diethylenetriamine (DETA) as main raw materials and employing a one-pot method to perform Michael addition polymerization reaction. By coupling polyethylene glycol (PEG) and folic acid (FA) with degradable hyperbranched polyamidoamine, folic-acid-targeted PEGylated degradable hyperbranched polyamidoamine is obtained. The raw materials are easily available, the preparation method is simple, and the prepared polymer medicine carrier has the advantages of hyperbranched polyamidoamine, such as three-dimension branching structure, a lot of cavities at the interior of molecules, low viscosity, a lot of functional groups, simple preparation method, biodegradability, and the like. Additionally, the water solubility and the stability of the carrier material are improved by grafting a PEG chain segment to the terminal, and the carrier is endowed with active targeting property on tumor cells through coupling of FA.