Development of porous silicon-based drug delivery systems for theranostics requires a precise control of their biodegradation. Thus, we propose a model for the biodegradation of porous silicon nanoparticles (PSi NPs) based on a diffusion equation combined with Nernst-Brunner mass transfer equation describing the dissolution of silicon and formation of silicic acid (SA). The spatiotemporal distributions of PSi NP porosity and SA concentration were calculated. The model was successfully applied to fitting a great variety of experimental data on more than 10 factors influencing the PSi NP biodegradation kinetics, such as the morphology of PSi NPs, surface composition, properties of surrounding media and protective coating layer. Two principal regimes were found out for systems with either diffusion or dissolution dominating over each other. The results of simulations revealed the values of several important parameters, which are hard to be measured experimentally.