This study focuses on the characteristics of fractured and vuggy high-temperature and high-salt reservoirs in the Tahe Oilfield. The Acrylamide/2-acrylamide-2-methylpropanesulfonic copolymer salt was selected as a polymer; the hydroquinone and hexamethylene tetramine was selected as the crosslinking agent with a ratio of 1:1; the nanoparticle SiO2was selected, and its dosage was optimized to 0.3%; Additionally, a novel nanoparticle coupling polymer gel was independently synthesized. The surface of the gel was a three-dimensional network structure, with grids arranged in pieces and interlaced with each other, and the structure was very stable. The SiO2nanoparticles were attached to the gel skeleton, forming effective coupling and enhancing the strength of the gel skeleton. To solve the problem of complex gel preparation and transportation, the novel gel is compressed, pelletized, and dried into expanded particles through industrial granulation, and the disadvantage of the rapid expansion of expanded particles is optimized through physical film coating treatment. Finally, a novel nanoparticle coupling expanded granule plugging agent was developed. Evaluation of the performance of the novel nanoparticle coupling expanded granule plugging agent. With an increase in temperature and mineralization, the expansion multiplier of granules decreases; aged under high-temperature and high-salt conditions for 30 days, the expansion multiplier of granules can still reach 3.5 times, the toughness index is 1.61, and the long-term stability of the granules can be good; the water plugging rate of granules is 97.84%, which is superior to other widely used particle-based plugging agents.