Bioceramic nanoparticles exhibit excellent features that enable them to function as an ideal material for hard tissue engineering. However, to fully understand their behavior, it is of crucial importance to understand their behavior within the fluids of the human body. To achieve this goal, we have studied the interaction between hydroxyapatite nanorods (HA) and bovine serum albumin (BSA). First, we describe the surface morphology of the nanoparticle. Then, the main characteristics of the physiological interplay of BSA and the hydroxyapatite nanoparticle are presented by using a battery of techniques: ITC, zeta potential, UV-vis, fluorescence, and CD. Experimental data was analyzed by developing specific approaches to determining important parameters such as rates, affinities, and stochiometries of protein associated with the nanoparticles. ITC has been confirmed as a powerful technique for determining the affinity, binding, and thermodynamics of BSA-nanoparticle interactions. Careful quantitative assessment of the kinetic properties of the adsorption were revealed by UV-vis and fluorescence measurements. Finally, CD measurements highlight the important role of protein flexibility in these kinds of systems.