Abstract: Accurate localization of radioactive material is essential for finding “orphan sources”, decontaminating and decommissioning nuclear facilities, and optimizing radiation protection. Silicon photomultiplier (SiPM) has been widely used in scintillator detection systems. To realize a low-cost large-field-of-view high-resolution detection system, a mixed-mode readout circuit combining a resistive network, a preamplifier circuit and an ASIC module was designed and verified. Firstly, by changing the rising edge, falling edge, pulse width and amplitude of the input pulse, the requirements of the A5202 module on the input pulse were experimentally measured to achieve the best data acquisition performance. When the rise time of the input pulse is less than 150 ns and the amplitude is greater than 20 mV, the data measured by the A5202 module have less noise and higher energy resolution. Then simulation was carried out by Multisim software. This simulation analyzed in detail the relationship between the resistor resistance and the rise time of the output signal. It determines the optimum resistor resistance value for the symmetric charged division circuit. The rise time of the output signal is relatively minimized when the resistance value of the first stage shunt resistor is 1 kΩ and the resistance value of the second stage shunt resistor is 100 Ω. Finally, in order to simultaneously take into account the characteristics of the output signal of the symmetric charged division circuit and the requirements of the A5202 module for the input signal, an inverse proportional operational amplifier circuit with the AD8066ARZ chip as the core was designed. It is used to connect the A5202 module and the symmetric charged division circuit. After the scintillator detection system was assembled, the stability of the system was examined, then the RMS noise of the system was measured, and finally the positioning accuracy of the system was examined. In order to improve the robustness of localization, the localization threshold was first calibrated with single lutetium-yttrium oxyorthosilicate scintillation (LYSO). The LYSO was further replaced with an array of cerium-doped gadolinium aluminum gallium garnet (GAGG(Ce)) crystals and the calibration results were examined with a ²⁴¹Am source. The test results show that the readout circuit has an RMS noise of about 2.73 mV. The location of the ²⁴¹Am source can be measured accurately, and the correct localization rate is about 90.87%. The readout circuit designed in this paper simplifies the 64-channel SiPM signal into 4 channels, and reduces the number of detector output signal channels by 16 times. A single ASIC module can read out 1024 SiPMs at the same time, which can greatly reduce the cost of readout for large-area SiPM arrays.