In this work, Ni-Co alloy nanoparticles (NPs) on La-doped SiO2 showed excellent selectivity toward ethanol for direct ethanol synthesis via CO hydrogenation. Over the catalyst with an optimal ratio of Ni/Co, the total alcohol selectivity reached 33.5%, of which ethanol occupied 47.0 wt %. The results demonstrated that the interaction between Co and Ni improved the ability to activate H-2 and CO and adjusted the amount of the dissociatively and associatively adsorbed CO. Besides, the mutual dilution of nickel and cobalt in Ni-Co alloy NPs effectively reduced the isolated Co or Ni-clusters; thus, the formation of heavy hydrocarbons was suppressed. In the reaction process, Ni@Co-Co2C, a core-shell composite with a nickel core and Co-Co2C shell, was formed, which suppressed the loss of nickel species. Moreover, with the reaction going on, a small amount of poorly alloyed Co-clusters would be covered gradually by the formed coke, resulting in an increase in alcohol selectivity.