The intrinsic exothermic reaction of coal with oxygen during low-temperature oxidation is the main heat source responsible for the self-heating and spontaneous combustion of coal. Due to the complexity of low-temperature oxidation of coal with many parallel reactions, it is difficult to directly investigate the heat evolution due to the reaction of coal with oxygen by conventional analytical method. Differential scanning calorimeter (DSC) was introduced in this study to study the intrinsic exothermic reaction of coal with oxygen based on the heat evolution. Using the subtraction analysis method of DSC, the DSC-subtraction curves can be obtained by subtracting the DSC���N2 curves from the DSC-air curves. Experimental results indicate that the DSC-subtraction curve can better reflect the intrinsic exothermic reaction of coal oxidation than a DSC-air curve by eliminating the influence of evaporation of water and thermal decomposition of inherent functional groups. The experiment factors affecting the intrinsic reaction were also investigated with the subtraction method of DSC. In terms of the kinetics characteristics of heat evolution, the intrinsic reaction of coal with oxygen is divided into three stages: slow oxidation stage, advanced oxidation stage, and rapid oxidation stage. The activation energies and pre-exponent factors at each of the stages were also calculated by oxidative pyrolysis kinetics. The subtraction method applied in this study is a quite promising method to determine the susceptibility of coal to self-heating and spontaneous combustion.