Abstract: In this work, a self-developed varied diffusion angle Venturi-type hydrodynamic cavitation generator was used to sterilize the raw water sample, taken from the Shangtang River of Hangzhou and blended with pathogenic microorganisms of different contents. Its killing effect was characterized by detecting the killing rates of total colony count and Escherichia coli, both as indicative microbes, and the study focused on the effects of Venturi diffusion angle and throat velocity, raw water percentage, cavitation number, and cavitation time on the killing rates. Results show that the killing effect can be improved by using appropriate raw water percentage and diffusion angle, increasing Venturi throat velocity, lowering cavitation number, or improving cavitation time. And hydrodynamic cavitation is an effective way to kill pathogenic microorganisms in raw water, thereby providing a safe, efficient and novel technology for drinking water disinfection without adverse by-products.