In this paper, a high-resolution interface circuit for resistive gas sensor is proposed. The circuit is based on resistance-to-frequency conversion which uses a buffer to keep the voltage across the gas sensor unchanged in order to eliminate the influence of voltage change on sensing material. The circuit has been fabricated in a 0.18 um CMOS technology with 1.8 V power supply. The area of the chip including PAD is only 640 um × 550 um. The experimental results report that the Pearson Correlation Coefficient is 0.99998 between the period of output signal and resistance when the measured resistance range is 500 Ω to 10 MΩ with corresponding signal frequency range of 1.23 MHz to 137 Hz. The interface circuit can detect the minimum change of 1 Ω resistance at a measured resistance of 500 Ω and 8.5 KΩ resistance at a measured resistance of 10 MΩ. For static gas, the chip can detect the ethanol gas concentration of 0 to 200 ppm and can detect a gas concentration change of 20 ppb at a low concentration.