As an important model. reaction, photocatalytic methanol dissociation on rutile TiO2(110) has drawn much attention, but its reaction mechanism remains elusive. Using DFT+U calculations, we investigate the whole dissociation process of methanol into formaldehyde with and without photogenerated holes, aiming to illustrate how the hole is involved in the dissociation. We find that the O-H dissociation of methanol is a heterolytic cleavage process and is likely to be thermally driven; the presence of a hole has no promotion on the barrier and enthalpy change. In contrast, the subsequent C-H bond cleavage follows the homolytic cleavage mode and is likely to be photochemically driven; great enhancement can be made in both kinetics and thermodynamics when holes are introduced. The essential roles of holes in promoting C-H dissociation are identified, and what kinds of catalytic reactions can or cannot be facilitated by holes is discussed. Our findings may considerably broaden the understanding of photocatalytic chemistry.