Nd2Zr2O7 pyrochlore with higher physicochemical and radiation stability has been considered as a host matrix for actinide immobilization of high level radioactive wastes. Uranium is a constituent and the decay-daughter product of high level radioactive wastes. It is necessary to study the solubility and ion-irradiation effect of uranium in Nd2Zr2O7 pyrochlore. The solubility of U is studied by the A site substitution in the pyrochlore structure. A series of uranium-doped zirconate pyrochlore compositions is prepared by the sol-gel-spray pyrolysis-high temperature sintering method. The structures of immobilization are studied by using X-ray diffraction (XRD) and Raman spectroscopy. The XRD and Raman spectroscopy studies reveal that the solubility limit of uranium in Nd2Zr2O7 is estimated at 10 at%. The lattice parameter of pyrochlore decreases with U content increasing, which is due to lower ionic radius of U. The immobilization structure changes from order pyrochlore to disorder structure. Further addition of U content leads to the separation of U3O8 phase in the immobilization. The U ions with high valance may be substituted at A or B site in Nd2Zr2O7 pyrochlore, which results in the A–O and B–O bond destruction. In order to keep the balance of charge, extra O ions should enter into the vacancy site, the structure of pyrochlore maybe transforms into a disorder structure. The radiation resistance of immobilization is investigated by ion-beam irradiation with 2 MeV Kr15+ ions at room temperature. The Nd2Zr2O7 and Nd1.9U0.1Zr2O7 are irradiated at doses of 1 dpa and 3 dpa, respectively. Analyses of the XRD and Raman spectroscopy data show that the Nd2Zr2O7 pyrochlore remains full pyrochlore structure even at a higher irradiation dose, which suggests that the Nd2Zr2O7 exhibits higher radiation resistance as potential immobilization. In contrast, the Nd1.9U0.1Zr2O7 immobilization shows the weaker radiation resistance, the pyrochlore structure completely transforms into a disorder fluorite structure. The A–O and B–O bonds of Nd1.9U0.1Zr2O7 pyrochlore structure are easy to destroy under ion irradiation conditions due to the disorder of pyrochlore. At the same time, the excess O ions are rearranged in U-rich pyrochlore after irradiation. Bond destruction and ion rearrangement of pyrochlore structure result in the full disorder fluorite structure. The actinides-doped pyrochlore structure is modified due to the change in physicochemical propertyof actinide, which results in the reductionof the solubility limit and radiation resistance.