Polyacrylamide (PAM)-silica microspheres with core-shell structure are synthesized by inverse microemulsion polymerization in this study for the application of water shut-off due to high strength of nanosilica, crosslinked shell of PAM and strong interaction between PAM and silica. The core-shell microspheres flow into the high permeable layers along with injected water, meanwhile, swell after absorbing water and migrate into the deeper layer under the pressure by deformation, which efficiently increase the pressure of low and medium permeable layers, and decrease the loss of water into high permeable layers. Most resources of crude oil locate in low and medium permeable layers, and this work plays a very important role in the enhancement of recovery ratio of crude oil by new material. Transmission electron microscope (TEM), digital microscopes, dynamic light scattering (DLS), and thermogravimetric analysis (TGA) are used to study the shape, size and high temperature resistant of the microsphere. Moreover, capillary flow experiments, nuclear-pore film filtration, and sand packed tube displacement experiment are applied to analysis the mechanisms of deep profile control.