The chemical effect of hydrodynamic cavitation (HC) in a Venturi reactor from both the theoretical and the experimental point of view is dealt. A mathematical model is presented to simulate the global production of hydroxyl radicals; it is based on a set of ordinary differential equations that account for the hydrodynamics, mass diffusion, heat exchange, and chemical reactions inside the bubbles. Experimentally, the degradation of p-nitrophenol (initial concentration 0.15 g dm-3) has been conducted in a lab scale Venturi reactor at inlet pressure ranging from 0.2 to 0.6 MPa and has been used to estimate the hydroxyl radical production. The optimum configuration, suggested by numerical simulations, has been experimentally confirmed. Thanks to the empirical validation, this novel modeling approach can be considered as a theoretical tool to identify the best configuration of HC operating parameters. (c) 2014 American Institute of Chemical Engineers