For the first time, hydrodynamic cavitation induced by a liquid whistle reactor (LWR) has been used in conjunction with the advanced Fenton process (AFP) for the treatment of real industrial wastewater. Semi-batch experiments in the LWR were designed to investigate the performance of the process for two different industrial wastewater samples. The effect of various operating parameters such as pressure, H2O2 concentration and the initial concentration of industrial wastewater samples on the extent of mineralization as measured by total organic carbon (TOC) content have been studied with the aim of maximizing the extent of degradation. It has been observed that higher pressures, sequential addition of hydrogen peroxide at higher loadings and lower concentration of the effluent are more favourable for a rapid TOC mineralization. In general, the novel combination of hydrodynamic cavitation with AFP results in about 60–80% removal of TOC under optimized conditions depending on the type of industrial effluent samples. The combination described herein is most useful for treatment of bio-refractory materials where the diminution in toxicity can be achieved up to a certain level and then conventional biological oxidation can be employed for final treatment. The present work is the first to report the use of a hydrodynamic cavitation technique for real industrial wastewater treatment.