Nanoparticles in biological media form dynamic entities as a result of competitive adsorption of proteins on nanoparticle surfaces called protein coronas. The protein affinity toward nanoparticle surfaces potentially depends on the constituent amino acid side chains which are on the protein exterior and thus exposed to the solution and available for interaction. Therefore, studying the adsorption of individual amino acids on nanoparticle surfaces can provide valuable insights into the overall evolution of nanoparticles in solution and the protein corona that forms. In the current study, the surface adsorption of l-histidine on TiO2 nanoparticles with a diameter of 5 nm at pH 7.4 (physiological pH) is studied from both macroscopic and molecular perspectives. Quantitative adsorption measurements of l-histidine on 5 nm TiO2 particles yield maximum adsorption coverage of 6.2 ± 0.3 × 10(13) molecules cm(-2) at 293 K and pH 7.4. These quantitative adsorption measurements also yield values for the equilibrium constant and free energy of adsorption of K = 4.3 ± 0.5 × 10(2) L mol(-1) and ΔG = -14.8 ± 0.3 kJ mol(-1), respectively. Detailed analysis of the adsorption between histidine and 5 nm TiO2 nanoparticle surfaces with attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy indicates both the imidazole side chain and the amine group interacting with the nanoparticle surface and the adsorption to be reversible. The adsorption results in no change in surface charge and therefore does not change nanoparticle-nanoparticle interactions and thus aggregation behavior of these 5 nm TiO2 nanoparticles in aqueous solution.