Abstract: Chlorination of raw water is a traditional technology for drinking water disinfection. However, recent studies have shown that chlorination generates byproducts DBPs as a result of chlorine reacting with organic compounds in water. The most common DBPs are THMs, HAAs and other harmful compounds, and all of them are carcinogenic, teratogenic and mutagenic, severely threatening human health. To explore new technologies of water disinfection, this paper describes an experimental study on disinfection of Escherichia coli, an indicator culture of pathogenic microorganisms, by using plates of square-shape multi-orifices as reactors of hydrodynamic cavitation. An agar plate colony-counting method was used for determination of the concentration of Escherichia coli in water samples taken from the flows behind the orifice plates, in the conditions of different orifice velocities, different orifice geometric parameters, and different initial concentrations of Escherichia coli. Our analysis focused on variations in the killing rate of Escherichia coli with several factors: cavitation number, orifice velocity, initial concentration, number and size of orifices on the plate, and arrangement of the orifices. The results show that killing rate can be increased by enhancing velocity, choosing appropriate initial concentration, improving treatment time, or increasing the number or decreasing the size of orifices. Hydrodynamic cavitation produces significant killing effect on Escherichia coli and it can serve as a new disinfection technology for further study.