Based on the skeleton structure and surface group characteristics of coal samples, molecular model of the key active groups for coal spontaneous combustion were constructed in this chapter. Based on density functional theory (DFT), the electrostatic potential distribution and active center of reaction were simulated and calculated. Then, importance of reactive groups such as hydroxyl, carbonyl and methyl groups in the coal spontaneous combustion were emphasized. Hence, active sites of coal molecules could be more accurately predicted. Furthermore, weak interaction mechanisms between the molecular structure of the extractant and the active group molecules were analyzed by optimizing the extractants.