Starting from the position of coal and the distribution of coal resources in the global and Chinese energy structure, this chapter analyzed the major threaten of coal fires for the safety production of coal mines resulted by coal spontaneous combustion, and emphasized the importance and urgency of studying mechanism of coal spontaneous combustion. Advances on mechanism of coal spontaneous combustion including the bacterial action theory, the pyrite theory, the phenol-based action theory and the coal-oxygen composite theory have been analyzed systematically. More importantly, advantages of the coal-oxygen composite theory as well as its unsolved problems such as oxidation pathway of active groups, reaction conditions, microstructure evolution law, etc. were analyzed. Aiming at research bottleneck due to extremely complex of coal molecular structure, this chapter proposed a new idea to investigate mechanism of coal spontaneous combustion by employing ultrasonic extraction technology combined with molecular dynamics simulation method.