This research aims to evaluate the performance of hybrid method of ozonation and hydrodynamic cavitation with orifice plate on E.coli bacteria disinfection. In this research, ozone dose, circulation flowrate, and disinfection method were varied. Ozone was produced by commercial ozonator with ozone dose of 64.83 mg/hour, 108.18 mg/hour, and 135.04 mg/hour. Meanwhile, hydrodynamic cavitation was generated by an orifice plate. The disinfection method compared in this research were: hydrodynamic cavitation, ozonation, and the combination of both. The best result on each method was achieved on the 60th minutes and with a circulation flowrate of 7 L/min. The hybrid method attained final concentration of 0 CFU/mL from the initial concentration of 2.10 × 105 CFU/mL. The ozonation method attained final concentration of 0 CFU/mL from the initial concentration of 1.32 × 105 CFU/mL. Cavitation method gives the least disinfection with final concentration of 5.20 × 104 CFU/mL from the initial concentration of 2.17 × 105 CFU/mL. In conclusion, hybrid method gives a faster and better disinfection of E.coli than each method on its own.