It is imperative to have an in-depth understanding of the intrinsic reaction between coal and oxygen during low-temperature oxidation, as the reaction is the main source responsible for the self-heating and spontaneous combustion of coal. As low-temperature oxidation of coal involves a series of physical and chemical process and many parallel reactions, it is difficult to directly investigate the intrinsic reaction between coal and oxygen by conventional analytical method. Thermogravimetric analysis (TGA) was used to investigate the intrinsic reaction between coal and oxygen based on the mass change. By means of the subtraction analysis method of TGA, the TG-subtraction curves were obtained by subtracting the TG-N2 curves from the TG-air curves. The results indicate that a TG-subtraction curve can better reflect the intrinsic reaction of coal oxidation than a TG-air curve by eliminating the influence of evaporation of water and thermal decomposition of inherent oxygen-containing groups. In terms of the rate of mass increase, the intrinsic reactions can be divided into three stages: slow oxidation stage, advanced oxidation stage and rapid oxidation stage. The activation energy at each of the stages, obtained by Coats and Redfern’s model, can be used to as a technical parameter to evaluate the proneness of coal spontaneous combustion. The optimum experiment conditions were also developed to study low-temperature coal oxidation with the subtraction method of TGA.