A hydro-cyclone was applied to the separation of gypsum, a byproduct of the wet limestone gypsum flue gas desulfurization (FGD) process, that uses limestone as the raw material. Using a high slurry concentration, similar to that used in an actual plant, the effect of the inlet shape and ceiling clearance of the hydro-cyclone was examined, and a model for predicting the efficiency of separation is proposed. The results indicate that the 50% cut size decreases when the inlet width ratio is decreased. Over the entire range of inlet width ratio, the limestone content of the blow-down flow decreased by approximately half, compared with that of the feed, and it was confirmed the purity of the gypsum could be improved by decreasing the limestone content. When the ceiling clearance of the hydro-cyclone was changed, an optimum ceiling clearance for obtaining a minimal cut size was found. A model for predicting the slurry concentration that is proportional to the solid throughput of a hydro-cyclone and the improvement in gypsum purity in an actual plant is proposed. The results of this calculation model agreed well with experiment data.