We present a feasibility study of the homogenization of pressurized water reactor spent nuclear fuel (SNF) powder through a mechanical mixing process. Because burn-up of the SNF depends on the position in the SNF assembly, concentrations of uranium, plutonium, and fission products are distributed differently according to the burn-up profile. The heterogeneity of the material elements affects the selection of a representative sample for quantitative analysis. Homogenization process improvement to reduce the sampling error is thus required to precisely determine the amount of uranium, plutonium, and fission products in the SNF. In this study, fine powders (<70 μm) extracted from one SNF rod were mixed, and the degree of homogenization was determined as a function of the mixing time indicating the relative standard deviations of the 134Cs/137Cs, Pu, and U isotope ratio measurements.