The 16N monitoring system operates in a mixed neutron-gamma radiation field and is subject to high background radiation, thus triggering instability in the 16N monitoring system measurement data. Due to its property of actual physical process simulation, the Monte Carlo method was adopted to establish the model of the 16N monitoring system and design a structure-functionally integrated shield to realize neutron-gamma mixed radiation shielding. First, the optimal shielding layer with a thickness of 4 cm was determined in this working environment, which had a significant shielding effect on the background radiation and improved the measurement of the characteristic energy spectrum and the shielding effect on neutrons was better than gamma shielding with the increase in the shield thickness. Then, functional fillers such as B, Gd, W, and Pb were added to the matrix to compare the shielding rates of three matrix materials of polyethylene, epoxy resin, and 6061 aluminum alloy at 1 MeV neutron and gamma energy. The shielding performance of epoxy resin as the matrix material was better than that of the aluminum alloy and polyethylene, and the shielding rate of boron-containing epoxy resin was 44.8%. The γ-ray mass attenuation coefficients of lead and tungsten in the three matrix materials were simulated to determine the best material for the gamma shielding performance. Finally, the optimal materials for neutron shielding and gamma shielding were combined, and the shielding performance of single-layer shielding and double-layer shielding in mixed radiation field was compared. The optimal shielding material-boron-containing epoxy resin was determined as the shielding layer of the 16N monitoring system to realize the integration of structure and function, which provides a theoretical basis for the selection of shielding materials in a special working environment.