Pneumatic technology takes compressed gas as the power source, but the leakage of gas in the pipeline due to poor sealing or pipeline rupture affects the accuracy of pneumatic control, the flow of gas transmission, and even the emission of harmful gas. The air tightness of differential pressure method has broad significance in the study of tight leakage because of its simple operation, short detection time, and high precision. Bubbling method, acoustic emission detection method, and direct pressure detection method have the characteristics of difficult operation, environmental sensitivity and low detection accuracy. They are not suitable for effective and high-precision detection of leakage in harsh environment. The air tightness detection method of differential pressure method has the advantages of simple operation, short detection time, and high accuracy. It has extensive significance in the research of air tightness leakage. At present, the focus of differential pressure method is to keep the same charging state of the master tank and the tested tank. However, when the shape of the tested tank is irregular or difficult to copy, the influence of different master tank on differential pressure method leakage detection needs to be considered. In this study, a gas leakage flow calculation model is established. The influence of the inherent parameters of the master tank on the calculation of the pressure difference, temperature difference, and leakage between the two cavities is analyzed in the simulation. Finally, the master tank is set as a quasi-isothermal cavity, and the tested tank is set as 3 L and 5 L air tanks for leakage test. The maximum error of experiment of 3 L tank reaches 39 mL/min at the later stage of measurement, with a detection deviation of 14.4%. The maximum error of experiment of 5 L tank is 412.4 mL/min, with a deviation rate of 28.3%. This method can detect leakage with high precision in harsh environment.