The invention discloses a resistance high-precision measuring system and method with combination of a differential method and a proportion method. The system comprises a constant current source, a reference resistor, a first differential amplifier, a programmable gain amplifier, an analog-to-digital converter, a microprocessor, a digital-analog converter and a measured resistor interface, the measured resistor interface is connected to a measured resistor, the reference resistor and the measured resistor are connected in series to form a serial connection branch circuit connected between the constant current source and the ground, two input terminals of the first differential amplifier are respectively connected with two terminals of the reference resistor, an output terminal of the firstdifferential amplifier is connected with a voltage reference terminal of the analog-to-digital converter, a first input terminal of the programmable gain amplifier is used for being connected to a to-ground single-end voltage of the measured resistor, a second input terminal of the programmable gain amplifier is connected with an analog output terminal of the digital-to-analog converter or the ground in a controlled manner, an output terminal of the programmable gain amplifier is connected with an analog input terminal of the analog-to-digital converter, and digital output terminals of the analog-to-digital converter and the digital-to-analog converter are both connected with the microprocessor. According to the system, the influence of power supply fluctuation can be overcome, the cost islow, and the measuring precision is high.