Hydrocyclones are widely used in industry, of which the geometrical design using CFD techniques is gaining more popularity in recent years. In this study, the Euler-Euler approach and the Reynolds stress model are applied to simulate the liquid-solid flowfield in a hydrocyclone. The methodology is validated by a good agreement between experimental data and numerical results. Within the research range, the simulation indicates that the liquid-solid separation mainly occurs in the conical segment, and increasing conical height or decreasing cylindrical height helps to improve the grade efficiencies of solid particles. Based on these results, two of the same hydrocyclones are designed and installed in series to establish a liquid-solid separation system. Many experiments are then conducted under different conditions, in which the effects of the water cut and the second hydrocyclone on the separation are investigated. The results also confirm that smaller solid particles are more susceptible to the inlet conditions, and the second hydrocyclone plays a more important role as the water cut reduces.