In this research, the modeling of Cu0.4Zn0.6Al2O4 catalysts performance and optimizing of esterification reactions were considered by the central composite design (RSM) response method. The main independent parameters of temperature, the ratio of alcohol to oil, the amount of catalyst and time duration have been considered for setting the esterification process. To access the maximum activity in the esterification process, the optimum conditions are estimated at 10.42 the molar ratio of alcohol to oil, 2.98 wt.% for the amount of catalyst at the temperature of 163.37 degrees C and within 4.15 hrs. Under these conditions, the conversion will be above 97.94%. These conditions have been applied to adjust the process of transesterification of waste cooking oil. The reusability of the Cu0.4Zn0.6Al2O4 nanocatalyst in the esterification reaction was investigated in this study. Employed statistical techniques and developed models can be employed as a useful tool for design, prediction, and optimization of the biodiesel production process with effective performance for various industrial applications. (c) 2021 Society of Chemical Industry (SCI).