In this work, the influence of particle size and surface functional groups on the adsorption behavior of bovine serum albumin (BSA) by three types of oxide nanoparticles (NPs), TiO2 (50 ± 5 nm), SiO2(30 ± 5 nm), and Al2O3 (150 ± 5 nm for α type and 60 ± 5 nm for γ type) was investigated in deionized water, in order to explore their interaction mechanisms without competitive influence of other ions. Bulkparticles (BPs) were also used for comparison with NPs. BSA adsorption maxima on oxide particles were controlled by the surface area and hydrogen content, while adsorption process was primarily induced by electrostatic interaction, hydrophobic interaction and ligand exchange between BSA and oxide surfaces. With the increase of hydrogen content, the BSA adsorption mechanism switched from mainly hydrophobic interaction to hydrogen bonding and ligand exchange. Calculations, based on surface area and BSA size, suggested that a multilayer of BSA covered on α-Al2O3, and single layer on the other oxide particle surfaces. BPs led to greater conformational change of BSA molecules after the adsorption on the surfaces of oxide particles though NPs adsorbed more BSA than BPs.