A novel approach of ozone treatment assisted by a liquid whistle reactor (LWR), which generates hydrodynamic cavitation, has been explored for water disinfection using a simulated effluent containing Escherichia coli (E. coli), one of the dominant markers in faecal coliforms. A suspension having an E. coli concentration of approximately 10 8 to 10 9 CFUmL −1 was introduced into the LWR to examine the effect of hydrodynamic cavitation alone and in combination with ozone. Operating conditions of inlet pressure and ozone doses as well as time of ozonation for individual operation along with the combined operation have been varied with the aim of maximizing the extent of disinfection and arriving at an optimum strategy for treatment. It has been observed that nearly 75% disinfection can be achieved in about 3h of treatment time using an optimized combination of hydrodynamic cavitation and ozonation. This combination has been found to be a cost-effective technique for achieving maximum disinfection compared to the individual operation of hydrodynamic cavitation (lower extent of disinfection) and ozonation (higher costs of treatment usually due to higher cost of ozone generation).