Abstract: The influence of matrix elements that usually exist in spent nuclear fuel reprocessing, such as Na, Al, Ru, Cs, Pd, Nd, Fe, Ce, Sr, Y, Mo, and Zr, on the determination of uranium by highly oriented pyrolytic graphite（HOPG） pre-diffraction EDXRF is studied. The results show that the influence of matrix elements Na, Fe, Al, Ru, Cs, Pd, Nd, and Ce is negligibly small when their mass concentrations are lower than 1000mg/L. The influence of matrix elements Sr, Y, Mo and Zr is somewhat greater, and can be corrected to some degree by correction with scattered line of the silver target if their mass concentrations are lower than 1000mg/L. For higher mass concentration of these elements, their influence can be corrected by extrapolation of their mass fraction to zero by using the linear relationship between the logarithm of the uranium line intensity and the mass fraction of these elements.