To realize a high-precision link in space optical communication， we analyzed key factors that affect the accuracy of flat-panel detectors in terms of target positioning. The error of the centroid algorithm was analyzed from the mechanism and the necessity of satisfying the spatial lossless sampling condition was verified by using a simulation. The defined NU value served as an indicator in quantifying the nonuniformity of the detector. As the NU value increased linearly， the positioning error of the centroid continued to increase， whereas the speed reduced. When the NU value was 0.005， the maximum positioning error was 0.043 pixels. Considering that the light intensity of the target incident on the optical system varies constantly， the smaller the NU value， the closer the centroid is to the true position of the light spot. Furthermore， the pixel response of a typical complementary metal oxide semiconductor （CMOS） detector was experimentally tested under different illumination intensities. Based on the response curve， a mathematical model for the nonuniformity of the pixel response was established. It can be determined that the NU value fluctuates from 0.0045 to 0.0048 within the linear response range. The experimental results of the spot centroid positioning accuracy verify that the absolute positioning error is less than 0.05 pixels， which satisfies the requirements of high-precision links. Therefore， the effectiveness of the theory and simulation presented in this study can be validated.