The experimental design and response surface methodology (RSM) have been applied to the investigation of the electro-UV complex process for the disinfection of E. coli in the water. The disinfection reactions of electro-UV process were mathematically described as a function of parameters power ($X_1$), NaCl dosage ($X_2$), initial pH ($X_3$) and disinfection time ($X_4$) being modeled by use of the Box-Behnken technique. The application of RSM using the Box-Behnken technique yielded the following regression equation, which is an empirical relationship between the residual E. coli number and test variables in actual variables: Ln (CFU) = 23.57 - 0.87 power - 1.87 NaCl dosage - 2.13 pH - 2.84 time - 0.09 power time - 0.07 NaCl dosage pH + 0.14 pH time + 0.03 $power^2$ + 0.47 NaCl $dosage^2$ + 0.20 $pH^2$+ 0.33 $time^2$. The model predictions agreed well with the experimentally observed result ($R^2$ = 0.9987). Graphical response surface and contour plots were used to locate the optimum point. The estimated ridge of maximum response and optimal conditions for the E. coli disinfection using canonical analysis was Ln 1.06 CFU (power, 15.40 W; NaCl dosage, 1.95 g/L, pH, 5.94 and time, 4.67 min). To confirm this optimum condition, the obtained number of the residual E. coli after three additional experiments were Ln 1.05, 1.10 and Ln 1.12. These values were within range of 0.62 (95% PI low)~1.50 (95% PI high), which indicated that conforming the reproducibility of the model.