In this study, a combined hydraulic cavitation device composed of a triangular multi-orifice plate and a Venturi Pipe developed by the Hydraulics Laboratory of Zhejiang University of Technology, was used to sterilize the pathogenic microorganisms in the raw water samples taken from the Shengli River in Hangzhou with different volume ratios. Escherichia coli and the total colony count were chosen as the indicator bacteria of the pathogenic microorganisms. The effects of diffusion angles of the Venturi tube diffusion section, number of orifices of the triangular multi-orifice plate, arrangement of the orifices, volume ratio of the raw water and the number of cavitation on the killing rates of pathogenic microorganisms were studied by the agar plate method. The experimental results show that choosing an appropriate diffusion angle and the raw water volume ratio, increasing the orifice number, using staggered orifice layout, and lowing the cavitation number can considerably increase the killing rates of the total colony count and Escherichia coli.