Bioactive ceramics, such as calcium phosphate and calcium sulfate, have gained attention with the increase of aged population. Contrast to bio-inert ceramics, such as alumina and zirconia, the strength of bioactive ceramics is much lower. The strength of calcium sulfate (CaSO4) is the lowest among all. In the present study, two approaches, involving the refinement of microstructure and the addition of nano-particles, are combined to enhance the strength. Various powder-processing treatments are adopted to facilitate these approaches. A pre-grinding treatment is applied first to reduce the matrix CaSO4 grain size. The nano-silica (SiO2) particles are then fixed onto the CaSO4 particles through an attrition milling process. The strength of CaSO4 is enhanced by 60% by adding only 1 mass% nano-SiO2 particles. The strength of the SiO2-CaSO4 composites follows the Orowan-Petch relationship, indicating that their strength is dominated by the flaws. The addition of nano-particles refines the matrix grain size, consequently, the flaw size. (C) 2020 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.