Periodic density function theory (DFT) and kinetic Monte Carlo (kMC) method are carried out to investigate CO dissociation process on the Mn-doped Fe(100) surface. The energetics information of relevant atomistic processes and adsorption features of relevant species are obtained from DFT calculations. Subsequently, kMC simulations are performed with DFT results employed as database. Simulations show that the energy barriers for CHO and COH formations are 0.09 eV and 0.35 eV larger than that for direct CO dissociation on Mn/Fe(100), respectively. An empty site is created with a CO hydrogenation (CO* + H* -> COH* + *, CO* + H* -> CHO* + *), while an active site is consumed with a CO direct dissociation (CO* + * -> C* + O*). The number of unoccupied active sites can affect the way of CO dissociation. On surfaces with considerable unoccupied active sites, direct CO dissociation mechanism is the preferred route. Under conditions favoring a very low number of unoccupied active sites and a mass of adsorbed H on surfaces, H-assisted CO dissociation via COH will take place. Graphic