It is difficult to profile the high temperature and high salinity heterogeneous reservoirs，and the ineffective water circulation in the high water-cut period is serious. In this paper， the temperature-resistant and salt-resistant poly （divinylbenzene-acrylamide）microspheres with particle diameter of 2.89—57.05 μm were prepared by emulsion polymerization with divinylbenzene and acrylamide as monomers by controlling the dosage of sorbitan monooleate span80. The surface morphology，thermal stability，dispersibility and expansibility in water and long-term thermal stability of the polymer microspheres were investigated，and the injection plugging and displacement experiments were carried out. The results showed that the temperature resistance of poly（divinylbenzene-acrylamide）microspheres was up to 370℃，and it had good dispersion performance in 2.69 × 105 mg/L mineralized water. The expansion rate of polymer microspheres with particle size of 10.81 μm was 12.85% after 24 hours at 90℃，and it had long-term thermal stability. In high temperature and high salt environment，the polymer microsphere with the particle size of 10.81 μm had good injectivity and sealing property in the core with the permeability of 1700 × 10-3 μm2； After water flooding，the injection mode of“microsphere profile control + CO2 flooding”could play the role in microsphere profile control and CO2 flooding more efficiently，and the oil displacement effect was better than that of“direct CO2 flooding”and “microsphere profile control + water flooding”，which could enhance oil recovery by 22.65% in high water cut period. Therefore，it is necessary to carry out“microsphere profile control + CO2 flooding”operations to enhance oil recovery during high water cut period in high-temperature and high-salt heterogeneous reservoirs.