For tight reservoirs, hydraulic fracturing is often used in the field to create high permeability channels to enhance oil recovery. Fracture conductivity has an important impact on the long-term production of oil and gas, and the fracture conductivity will change over time due to various factors such as closure pressure, proppant particle size, and rock slab properties in actual formations. The determination of the conductivity of fractures after compression generally requires a large number of experimental methods. In order to study the long-term variation of fracture conductivity, this paper focuses on the effects of closure pressure and proppant particle size on the long-term fracture conductivity, and the results show that the fracture conductivity decreases significantly with time, decreasing by 10–50% within 48 h. When the closing pressure increases to 60 MPa, the proppant is broken, making it more tightly arranged, and the conductivity decreases by 15–60%, so the gap between large and small particle size proppant is gradually narrowed. Based on a large number of experimental data, the nonlinear fitting method was used to obtain a prediction model of the long-term conductivity of fractures with different particle sizes and closing pressures. The prediction formula was compared with the laboratory measurement results, and the fit degree was 0.956, which basically met the needs of engineering applications. By considering the time into the prediction model, the trend of fracture conductivity over time can be obtained more comprehensively, which can provide guidance for the determination of reservoir conductivity and the optimization of proppant in the field.