AbstractMicrowave is of promising applications in various chemical and material processes, however, the interactions between the microwave and the molecules from atomistic scales are lack of understanding. ReaxFF reactive molecular dynamics simulations were carried out to get insights into the interactions between the microwave and polyacrylonitrile (PAN) during microwave heating. It was found that the temperature evolution of the system was dependent on the electric field strength and frequency of the microwave. The alternate change of the electric field of the microwave leads to the alternate fluctuation of the temperature. We surprisingly predicted the atomistic hot‐spot effect of microwave heating of PAN that the cyano groups were selectively heated. With an electric field intensity of 0.6 V Å‐1 and a frequency of 60 GHz, the temperature of the hot‐spot atoms was 300 and 500 K higher than the carbon and hydrogen atoms in the PAN backbone, respectively. We also analyzed the thermal runaway behavior of the system during microwave irradiations and found that it was attributed to the decomposition of PAN into smaller polar molecules. This work suggests that it is possible to selectively and effectively activate the cyano groups of PAN to improve their reactivity.