With the long-term water-flooding development of the reservoir, the non-homogeneity of the formation is increasing and the reservoir environment is deteriorating; the microspheres used for deep plugging have shown disadvantages, such as poor temperature and salt resistance and faster expansion. In this study, a polymeric microsphere was synthesized that is resistant to high temperature and high salt and can achieve slow expansion and slow release for deep migration. P(AA-AM-SA)@TiO2polymer gel/inorganic nanoparticle microspheres were prepared by reversed-phase microemulsion polymerization using acrylamide (AM) and acrylic acid (AA) as monomers, 3-methacryloxypropyltrimethoxysilane (KH-570)-modified TiO2as the inorganic core, and sodium alginate (SA) as a temperature-sensitive coating material. Through single-factor analysis of the polymerization process, the optimal synthesis conditions were determined as follows: the oil(Cyclohexane)-water volume ratio was 8:5, the emulsifier mass ratio (Span-80:Tween-80) was 3:1 (10 wt% of the total system amount), the stirring speed was 400 r/min, the reaction temperature was 60 °C, and the initiator (ammonium persulfate and sodium bisulfite) dosage was 0.6 wt%. The size of the dried polymer gel/inorganic nanoparticle microspheres prepared by the optimized synthesis conditions was 10~40 μm with uniform particle size. The observation of P(AA-AM-SA)@TiO2microspheres reveals that the Ca elements are uniformly distributed on the microspheres, and FT-IR indicates that the synthesized product is the target product. TGA shows that the polymer gel/inorganic nanoparticle microspheres have better thermal stability after the addition of TiO2, with a larger mass loss at 390 °C, which can adapt to the medium-high permeability reservoir environment. The thermal and aqueous salinity resistance of the P(AA-AM-SA)@TiO2microspheres was tested, and the cracking temperature of P(AA-AM-SA)@TiO2microsphere temperature-sensitive material was 90 °C. It still has favorable water absorption and swelling performance under the sodium salt concentration of 2.5 × 104mg/L and can tolerate calcium salt up to 2.0 × 104mg/L. Plugging Performance Test results show that the microspheres have good injectability between the permeability of 1.23 and 2.35 μm2and good plugging effect near the permeability of 2.20 μm2. At high temperature and high salinity, P(AA-AM-SA)@TiO2microspheres have a remarkable effect on profile control and water shutoff, the plugging rate reaches 95.3%, and the oil recovery rate is increased by 12.89% compared with water flooding, achieving the effect of slow swelling and slow release.