Abstract Although experimental studies have shown that Ga3Ni5 is a promising catalyst for carbon dioxide (CO2) hydrogenation to methanol (CH3OH), the roles that cluster size and support play in the reaction are not clear. This research was set to study the quantitative and qualitative impacts of the size and support of Ga-Ni clusters on CO2 hydrogenation to CH3OH at electronic and molecular levels by using density functional theory (DFT). Ga3Ni5, Ga6Ni10, Ga12Ni20, Ga15Ni25, and Ga24Ni40 nanoclusters, and γ-Al2O3- and SiO2- supported Ga6Ni10 were chosen as the study objects. Results show that adsorption energies of intermediates are highly related to intermediates’ characteristics and clusters’ active sites. Moreover, cluster size has no linear relation with the adsorption strengths of intermediates, while it has significant impact on the activation barrier of the rate-limiting step of hydrogenation process. Ga6Ni10 cluster has the lowest activation barrier of 1.04 eV due to the d-band center location and the exposed active sites of clusters. Compared with unsupported Ga6Ni10 clusters, Ga6Ni10/SiO2 and Ga6Ni10/γ-Al2O3 increase the adsorption energies of the intermediates and the activation barriers of the rate-limiting steps due to the lower electron transfer ability of Ga6Ni10 on SiO2 and γ-Al2O3 supports. Therefore, a support that can increase the electron transfer abilities of catalysts are preferable. The findings will be very beneficial for preparing new Ga-Ni catalysts for CO2 hydrogenation to CH3OH.