Adsorption kinetics and conformational changes of a model protein, bovine serum albumin (BSA, 0.1, 0.5, or 1.0 g/L), on the surface of hematite (α-Fe2O3) particles in 39 ± 9, 68 ± 9, and 103 ± 8 nm, respectively, were measured using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. As the particle size increases, the amount of adsorbed BSA decreases, but the loss in the helical structure of adsorbed BSA increases due to the stronger interaction forces between adsorbed BSA and the larger particles. On 39 or 68 nm hematite particles, refolding of adsorbed BSA can be induced by protein–protein interactions, when the protein surface coverage exceeds certain critical values. Two-dimensional correlation spectroscopy (2D-COS) analysis of time-dependent ATR-FTIR spectra indicate that the increase in the amount of adsorbed BSA occurs prior to the loss in the BSA helical structure in the initial stage of adsorption processes, whereas an opposite sequence of the changes to BSA conformation and surface coverage is observed during the subsequent refolding processes. Desorption experiments show that replacing the protein solution with water can quench the refolding, but not the unfolding, of adsorbed BSA. A kinetic model was proposed to quantitatively describe the interplay of adsorption kinetics and conformational change, as well as the effects of particle size and initial protein concentration on the rate constants of elementary steps in protein adsorption onto a mineral surface.