A novel approach that combines the indentation tests with nonlinear finite element modeling (FEM) is proposed to estimate the elastic/plastic constitutive relation of plasma-sprayed hydroxyapatite (HA) coatings on a Ti-6Al-4V substrate. The Ramberg-Osgood constitutive equation can well describe the deformation behavior of plasma-sprayed HA coating on Ti-6Al-4V. A reasonable estimation for the elastic modulus of the HA coatings is given, based on the fact that the coating consists of a crystalline phase, an amorphous phase and pores. The Ramberg-Osgood equations of the coatings indicate that the post-treatment increases both resistance to elastic and plastic deformation, but no effect on strain hardening behavior. The post-treatment, however, could reduce the resistance to coating/substrate separation. The influence of titanium substrate becomes more significant with decreasing coating thickness and increasing indentation load because the plasma-sprayed HA coatings exhibit much less resistance to indentation deformation than does Ti-6Al-4V.