This paper presents an interface scheme for the multiplexing transmission of multi-channel and two-wire sensor in the analog/digital signal circuit of the system. The scheme adopts the master-slave information transmission architecture, and the host unit can extend and connect up to 256 two-wire audio signal acquisition terminals. The intelligent audio signal acquisition terminal accepts the digital instruction of the main control unit online through signal multiplexing line technology while collecting the audio analog signal, and realizes the online programming, self-calibration and fault self-diagnosis functions of the audio signal acquisition terminal, which improves the information and intelligence level of the system to a great extent. This technology has been successfully applied to boiler pressure pipeline leak detection system.