Abstract: Aiming at the leakage problem in the compact sandstone drilling of the Keziluoyi Formation in Southwest Tarim, Nano-core-emulsion was prepared by coating modified nano-SiO2 with nano-emulsion, its particle size D50 is about 100 nm, with good dispersion stability. When 0.8% Nano-core-emulsion is added to 5% bentonite slurry, the fluid loss can be reduced by 40%, and the filter cake thickness can be reduced by 84%. Using a Nano-core-emulsion to optimize the plugging performance of potassium polysulfonate drilling fluid can reduce the fluid loss of the drilling fluid by 52%, the resulting filter cake is dense and tough, and the thickness is reduced by 40%. Using the pressure conduction method to evaluate the plugging rate, the plugging rate of the drilling fluid of the Nano-core-emulsion on the core of the Keziluoyi Formation is 63.4%, which is 20.9% higher than that of the field drilling fluid. According to microscopic examination and CT scanning analysis, the material has the plugging characteristics of “inner rigid support + outer soft deformation” and has demonstrated good field application results.