Advancing nanocatalytic therapies of tumors formed on non-toxic but catalytically active inorganic nanoparticles (NPs) have aroused great interest in tumor therapy recently, but the limited reactive oxygen species within tumors may limit treatment efficiency. Therefore, the combination of chemotherapy and chemodynamic therapy is a promising treatment strategy. Herein, poly(lactic acid-co-glycolic acid) (PLGA) grafted-γ-Fe2O3 nanoparticles (NPPLGA) with dual response of endogenous peroxidase (POD)- and catalase (CAT)-like activities has been reported. On the one hand, the NPPLGA could serve as a drug delivery system for doxorubicin (DOX), an anti-tumor drug used to treat lung adenocarcinoma A549 cells. On the other hand, based on the mimetic enzyme properties of NPPLGA, it can be combined with DOX to treat lung cancer. The results show that the NPPLGA could be simulated the CAT-like activity to decompose hydrogen peroxide (H2O2) into H2O and O2 under neutral tumor microenvironment, so as to reduce the oxidative damage caused by H2O2 to lung adenocarcinoma A549 cells. Under acidic microenvironment, NPPLGA could simulate POD-like activity to effectively catalyze the decomposition of H2O2 to produce highly toxic hydroxyl radicals (•OH) to induce the death of tumor-cell through regular catalytic reaction of Fenton. Furthermore, the POD-like activity of NPPLGA synergistic with DOX can promote the apoptosis and destruction of A549 cells and enhance the antitumor impact of DOX-NPPLGA. Therefore, this study provides an efficacious dual inorganic biomimetic nanozyme-based nanoplatform for lung tumor treatment.