Abstract: In order to investigate the evolution characteristics of the key groups and their thermal effects under the effect of oxygen-depleted, the thermal reaction process of coal under different oxygen concentrations and the change law of its microscopic groups were studied by using Differential Scanning Calorimetry experiments and in-situ Fourier Transform Infrared Spectroscopy experiments. The results indicate that the coal spontaneous combustion exothermic process can be divided into five stages: evaporation heat absorption, oxidation heat release, decomposition heat storage, combustion heat release, and burnout, and the groups can be categorized into four groups: aromatic hydrocarbon compounds, aliphatic hydrocarbon compounds, hydroxyl groups and carbon-oxygen groups. With the increase of reaction temperature, —C=C— in coal decreased gradually, aliphatic hydrocarbon compounds and carbon-oxygen groups first increased and then decreased, and hydroxyl groups showed a two-stage decreasing trend. With the decrease of oxygen concentration, the coal reaction heat flow curve and characteristic temperature shifted to the high temperature region, and the reaction intensity, heat release and exothermic characteristic parameters decreased. Oxygen did not change the laws of the coal spontaneous combustion exothermic process and variations of groups, but it would significantly affect its key temperature nodes. Further, the grey correlation and quantum chemical methods were used to determine the evolutionary characteristics of key groups and their reactive thermal effects. The results showed that the trend of the most key groups of exothermic process of coal spontaneous combustion at any oxygen concentration was —OH-1→—COO—→Ar—CH→Ar—CH, but the key groups were attributed to hydroxyl group → carbon-oxygen → aliphatic compound → carboxylic compound. The key groups and their attribution had not been changed in the exothermic process of coal spontaneous combustion in the oxygen-depleted state. The production of H₂O and CO during coal spontaneous combustion is a spontaneous exothermic reaction, whereas the reaction of C₂H₄ and C₂H₂ production is a non-spontaneous absorptive reaction, and the sensitivity of C₂H₄ and C₂H₂ as spontaneous combustion indicator gases is stronger than that of the first two. The C₂H₂ generation reaction is one of the key reasons for the emergence of a significant endothermic peak in the coal oxidation exothermic stage, and the combustion of aromatic hydrocarbons to produce CO and CO₂ is one of the main reasons for the intense exothermic process of coal combustion.