Dense medium cyclone (DMC) is a high-tonnage device that is widely used to upgrade run-of-mine coal in the 0.5–50mm size range. It is known that the performance of a DMC depends on the coal particle size distribution but quantitative relationships have not been established yet. In this work, the effect of the particle size distribution in a DMC is studied in detail using the combined Computational Fluid Dynamics (CFD) and Discrete Element Method (DEM). In particular, Johnson’s SB function, which is capable of representing a wide range of size distributions, is employed to describe the particle size distribution of coal. The function has two parameters, i.e., particle median size d0.5 and distribution parameter σj, for a given size range. It is found that for a constant σj, the operational head and medium differential decrease dramatically, and the separation efficiency deteriorates rapidly when d0.5 increases from 6 to 40mm. For a constant d0.5, the DMC performance is sensitive to σj, particularly when d0.5 and σj are small. Both the medium differential and split decrease at first and then almost remain constant as σj increases from 0.4 to 1.0, and the separation performance follows the similar trend as well. The simulation results are also analysed in terms of medium and particle flow patterns, particle–fluid, particle–particle and particle–wall interaction forces to elucidate the underlying mechanism. For example, the decrease of pressure gradient force and viscous drag force represents the loss of swirling energy and then contributes to the drop of operational pressure and worse separation efficiency. The results should be useful to better design and control DMC operations, particularly for various coal types with different particle size distributions.