In this paper, a direct co-precipitation method was used to prepare antimony-doped calcium fluoride nanopowders (NPs). The effects of reaction concentration, reaction medium and lanthanum doping on the properties of calcium fluoride NPs were investigated via a control variable method and the best preparation conditions was identified. The structural analysis of the powder materials prepared in this work were carried out by XRD, SEM, ICP and other test methods. By analyzing the experimental data, we found that the best performance of Eu-doped CaF2 NPs can be acquired under the reaction concentration of 1 mol/L in aqueous solution. In the same time, the NPs possess a high degree of dispersion with an average diameter of 22 nm, which is beneficial to the preparation of transparent Eu3+: CaF2 ceramics with excellent up-conversion luminescence. The results show that the grain size, the crystallinity of the NPs and the amount of Eu infiltration have a decreasing tendency with the increasing reaction concentration, while the degree of agglomeration of the NPs can be enhanced by increasing the reaction concentration.