The O-H/C-H scission of methanol on Pt clusters is a crucial step in direct methanol fuel cells (DMFCs) applications. The first dehydrogenation process of methanol on Ptnq clusters (n=5, 13, 19; q=0, +1, −1) in various charge states is studied. Our findings indicate that methanol adsorbs more easily on cationic Ptn+ than on neutral Ptn or anionic Ptn−. However, the adsorption capacity of methanol on Ptnq gradually decreases with increasing cluster size, especially for CH3OH on Ptn+, which decreases significantly (from −57.61 to −16.41 kcal/mol). Compared with Ptn and Ptn+, the energy barrier of O-H/C-H bond cleavage is significantly reduced by injecting an electron into Ptn to form Ptn−, and the activity of catalyst is improved. However, the energy barrier of O-H/C-H cleavage increases gradually with cluster size, leading to a decrease in catalytic activity. The effect of charge weakens as cluster size increases, and small clusters with injected electrons exhibit better catalytic activity.