Abstract: In this study, experimental tests on hydrodynamic cavitation for disinfection were conducted on a reactor of multi-orifice plates that was independently developed in the Hydraulics Laboratory at Zhejiang University of Technology, and Escherichia coli that is pathogenic microorganism, was chosen as indicator bacteria. We measured time-average pressures of the flow behind the multi-orifice plates using a pressure data acquisition system, and collected water samples in the process of cavitation. A number of Escherichia coli bacteria were cultured in an agar plate, and changes in morphology were observed using a biological microscope. This paper focuses on an analysis of the disinfection of Escherichia coli impacted by cavitation number, orifice velocity, initial concentrations, number of orifice, arrangement of orifice and size of orifice, along with a brief illustration of the bactericidal mechanism of Escherichia coli under the impact of hydrodynamic cavitation.