In recent years, the enthusiasm for deep space missions has remained unabated, resulting in continuous advancements in the research field of space environment and particles. Many instruments carried on these missions have conducted detection of pickup ions (PUIs) in the solar system. For those instruments, simulation is an effective means and a crucial step for their performance optimization and future operation in-orbit. It holds great significance for the instrument’s in-orbit performance assessment, science operation optimization, and detection efficiency enhancement. In this paper, the traditional probability model and the Vasyliunas and Siscoe (V–S) model are used to generate the PUIs, which are the input for the simulation of the PUI detector. For further analysis, the numerical results of the simulation are processed to calculate the instrument’s geometric factor, mass resolution, and count rates. Then, two sets of experiments are carried out for the comparison of the traditional probability model and the V–S model. The results show that, for the simulation of the instrument in the design stage, the simulation results of the traditional probability model and the V–S model are not much different. However, for the simulation of the instrument performance in-orbit, the PUI data generated based on the V–S model gave a better result than those of the traditional probability model. This conclusion is of great significance for evaluating the detection ability of the PUI detector in future deep space explorations.