As the manual centering of laser particle size analyzers is slow operation and difficult to be adjusted, this paper presents an automatic centering method for the 50-channel photo detector based on a four-quadrant detection unit. According to the different positions of the detectors, the process of automatic centering was divided into pre-centering and acute-centering. When the laser beam was out of the sensing range of the detector, the system carried out a pre-centering based on the special structure of the detector; When the laser beam could be sensed by the detector, the system undertook the acute-centering according to the photocurrent intensity from the detector to determine its motion direction. After transition from a pre-centering into the acute-centering, the variable step was used to obtain the best cut-off condition of the automatic centering system by comparing the centering accuracy and centering time. Furthermore, the designs of software and hardware of the laser size analyzer were completed and the reliability and accuracy of the system were verified. The results show that its resolution is higher than 5 μm. Finally, the method was used to test standard particles, and the data after automatic centering meet the requirements of calibration specification for static light scattering particle size analyzers.