Abstract: In this paper, the gamma ray shielding of depleted uranium is verified by experiment and simulation. A nuclear power pressurized water reactor shielding model is constructed, and the simulation distribution of neutron energy spectrum in the shielding layer was consistent with that in practice. The comprehensive shielding performance of depleted uranium in different positions of neutron and gamma mixed radiation field were simulated by the Monte Carlo simulation method and the fuel consumption calculation program, and compared with that of the lead shielding material. The activation and fission products of the depleted uranium irradiated by the shielding neutrons for 40a was simulated and calculated, and the radio-toxicity defined by Annual Limit of Intake (ALI) before and after irradiation of the material was analyzed. The results show that the addition of secondary products has little effect on the radio-toxicity.