In the non-invasive tissue composition detecting, the diffuse reflectance spectroscopy could be affected by the measurement conditions, especially the tissue deformation induced by the contact pressure. In this paper, the physical model was simulated to quantify the changes of tissue thickness, optical properties and diffuse reflectance induced by the contact pressure, respectively. Firstly, based on the physical complex model and solid-liquid mixture composition of biological tissue, the deformation and changes of the water under contact pressure were quantitatively analyzed. In this model, the skin tissue was modeled as the elastic structure filled with Newtonian fluid. Then, the finite element method was applied to simulate the time-varying deformation of tissue under certain contact pressure. Secondly, the scattering and absorption coefficients of tissue were calculated with the quantitative results of the deformation and water migration in the three-layered skin tissue. After that, Monte Carlo method was used to simulate the light propagation within the tissue under different pressures. Finally, the effective information contained in the diffuse reflectance spectrum was analyzed to quantify the influence of the contact pressure. The results showed that the reduction of thickness and water content in dermis resulted in the decrease of effective information contained in the diffuse reflectance spectrum. The conclusions of this paper are beneficial for optimizing measurement strategy and improving accuracy and repeatability of the in vivo diffuse spectroscopy measurements.