The CFD simulation of cyclone separators has remarkably evolved over the past decades. Nowadays, computational models are essential for designing, analyzing, and optimizing these devices. Due to the intrinsic anisotropy of the flow inside these separators, the Reynolds stress model (RSM) has been mostly employed. However, RSM models fail to solve most time and space scales, including those relevant to particle behavior. Consequently, the prediction of the grade collection efficiency may be hindered, particularly for low-Stokes-number particles. For example, the precessing vortex core phenomenon (PVC), a well-known phenomenon that is relevant for particle motion, is not usually captured in Reynolds-averaged Navier–Stokes (RANS) simulations. Alternatively, the large-eddy simulation (LES) has been proven to be a superior approach since it captures many time and space scales that would have been otherwise dissipated, allowing for more accurate predictions of particle collection. However, this accuracy comes at a considerable computational cost. To combine the advantages of these two models, the main objective of this research was to evaluate a new hybrid RSM-LES model applied to the cyclone’s flow. The results were compared to experimental data and with RSM model results. It showed that, compared to a RANS model given by the RSM closure model, the grade collection efficiency curve obtained by the hybrid model is closer to the experimental one, even for the coarser mesh. Beyond that, the results showed that while the improvement in results was not proportional to mesh refinement for RANS modeling, the hybrid model showed significant improvement with mesh refinement.