The invention discloses a device and method for measuring diffusion coefficients of variable-volume constant-pressure gas in liquid. The device mainly comprises a gas sample bottle, a gas cavity, a diffusion cavity, a thermostatic bath, a valve, a vacuum pump, a reducing valve, a displacement sensor, a pressure sensor, a platinum resistance thermometer and a data acquisition system, wherein the diffusion cavity adopts a visible window structure with quartz glass; the diffusion cavity is equipped with the pressure sensor and the displacement sensor; the pressure of the diffusion cavity is kept constantly by a movable piston and a pressure-controlled gas cylinder in the diffusion process; the movement distance of the movable piston in the measurement process is measured by the displacement sensor; diffusion data of the gas in the liquid are calculated and obtained through the Fick's second law. The device realizes measurement of diffusion data of the gas in the liquid at the constant pressure, and has the advantages of simple structure, low cost, convenience in operation and stable system.