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Nuclear quadruple resonance (NQR) has been studied for explosive detection for years. Some prototype NQR-based detection systems have been reported, but were all designed from the laboratory perspective, with bulky sizes and high power consumption. To achieve a portable NQR-based detection system for field applications, a low-power compact system utilizing state-of-the-art semiconductor technologies is presented in this paper. Several novel circuits for the key modules are proposed, including a Class-D type power amplifier, a power multiplexing and matching network, a customized IC with integrated analog signal processing chain, and a microcontroller-based logic control unit. An advanced digital signal processor platform is employed for data collecting and processing. The customized IC is fabricated in 0.18 μm CMOS process. Test results on the prototype system show the effectiveness of the proposed solution and low power consumption as 2.12 W in the receiving state. The power efficiency of the proposed transmitting section is higher than 60%.