Hydrocyclone has been widely used in particle separation processes. Extensive efforts have been devoted to studying the liquid–solid flow in conical hydrocyclone, however, studies on cylindrical hydrocyclone were much less, regardless of its industrial importance. To this end, an Eulerian–Lagrangian model, dense discrete phase model (DDPM), was used to simulate the complex liquid–solid flow in an industrial-scale cylindrical hydrocyclone, where Reynolds stress model (RSM) was used to model the turbulence of liquid phase due to its swirling nature, and then the numerical results were validated against the experimental data obtained from an industrial-scale cylindrical hydrocyclone. The validated model was then used to systematically study the effects of operating conditions as well as the geometry of cylindrical hydrocyclone on its separation efficiency. It was shown that (i) particle concentration at inlet had a remarkable influence on particle separation efficiency, but had a negligible effect upon processing capacity, expressed as the inlet volumetric flow rate of liquid–solid mixture; (ii) the increase of the length of vortex finder resulted in a slight decrease of separation efficiency and larger diameter of vortex finder led to increased mass flow rate through overflow and slightly decreased separation efficiency; (iii) increasing the height of cylindrical part resulted in a larger mass flow rate through underflow and better particle separation efficiency. Present studies indicated that DDPM method coupled with RSM was an effective tool for the design of liquid–solid hydrocyclone.