Hydrodynamic cavitation is a technology for the process intensification of a heterogeneous liquid-liquid system, which was applied for the preparation of epoxy Fatty Acid Methyl Ester (FAME) without sulfuric acid. Compared with mechanical stirring, it could provide better mass transfer rate in a liquid-liquid system, and the reaction time was reduced more significantly. The effect of the relevant operating parameters in the hydrodynamic cavitation reactor on the epoxidation of FMAE was studied. Operating parameters included the circulation rate, volume ratio of oil phase to aqueous phase, and upstream pressure. The results show that the higher circulation rate could result in much more cavitation times of the system, which favors the epoxy reaction. The optimized conversion of FAME is obtained when volume ratio of oil phase to aqueous phase is 2.4:1. The higher upstream pressure leads to a better emulsification and higher conversion of FAME. However, too much of the upstream pressure would result in the degradation of epoxy FAME.