Chemodynamic therapy (CDT) uses endogenous H₂O₂ of tumor cells to react with Fenton catalysts to generate highly toxic hydroxyl radical (•OH), thereby killing cancer cells. However, the insufficient endogenous H₂O₂ and low transport efficiency of nanoparticles result in unsatisfactory anticancer efficacy. Here, we successfully synthesized a Cu²⁺ doped mesoporous silica nanoparticles (Cu-MSN) with excellent dispersity and small size. After loaded with doxorubicin (DOX) and ascorbate (AA), Cu-MSN was coated with folic acid (FA), dimethyl maleic anhydride (DMMA) modified chitosan (FA-CS-DMMA) and carboxymethyl chitosan (CMC) to obtain a pH responsive targeted nanocatalyst FCDC@Cu-MSN@DA. SEM images showed that particle size of FCDC@Cu-MSN@DA was about 100 nm. After 48 h in vitro, cumulative amount of Cu²⁺ release reached 80% and DOX release was about 57.3% in the acidic environment. After oxidation of AA, the produced exogenous H₂O₂ induced Cu²⁺ to catalytic the Fenton-like reaction, which enhanced the therapeutic effect of tumor chemodynamic therapy (CDT). Cell experiments in vitro demonstrated that FCDC@Cu-MSN@DA exhibited excellent anticancer ability in the combination of CDT and chemotherapy. This multifunctional nanocatalyst has great potential application in cancer therapy in the future.