Polymer microparticles with various compositions and morphologies have recently received much attention. Their surface-roughness significantly affects the physical and chemical properties, which especially counts in regulating the interaction between biological materials and living systems. In this paper, we design a polystyrene microsphere with controllable surface textures. At first, a microfluidic device is used to generate droplets with uniform size containing the hydrophobic polymer and a co-surfactant. During the volatilization of the organic solvent, the shrinking droplets appear to be unstable at the interface. Thus, the surface area increases spontaneously, and microspheres with wrinkles on the surface are obtained after being solidified. The results show that tuning the concentration of the co-surfactant and the rate of solvent evaporation can effectively regulate the surface roughness of the microspheres. Circulating tumor cell capture experiments reveal that this textured structure can facilitate the cell adhesion and increase the number of the captured cells. These features indicate that the coarse microspheres possess a promising application prospect in the field of biomedical analysis.