The present research studied the anti-bacterial effect of silver-coated red soil nanoparticles on Gram-negative bacteria Escherichia coli (E. coli) from water. The effects of disinfectant concentration (0.02, 0.05 and 0.1 g/mL), contact time (10, 20 and 30 minutes) and bacteria number (102, 104 and 106 CFU/mL) have been also investigated. To obtain important factors, the interactions between factors and optimal experimental design in surface response method were used based on Box-Behnken design. According to the research findings, the system is efficient in eliminating E. coli. The results showed that E. coli elimination efficiency intensified through increasing the amount of disinfectant from 0.02 to 0.1 g/mL. Expanding contact time from 10 minutes to 30 minutes also heightened the E. coli elimination rate. R2 for E. coli elimination is 0.9956 indicating a good agreement between model experimental data and forecasting data.