Lithium silicate is one of the suitable heterogeneous catalysts for biodiesel production. The possibilities of large number of combinations of different reaction parameters make the optimization of biodiesel production process over various heterogeneous catalysts highly tedious, necessitating the development of alternate strategies for parameter optimization. Here, Box-Behnken design (BBD) coupled with response surface methodology (RSM) is employed to optimize the process parameters required for the production of biodiesel from waste cooking oil using lithium silicate as catalyst. Simple method of impregnation was performed for the material preparation and the catalyst was analyzed using different techniques. It was found that the activity is directly proportional to the basicity data obtained from temperature programmed desorption (TPD) of CO2 over various catalyst systems. The material exhibits macroporous morphology and the major crystalline phase of the most active catalyst was found to be Li2SiO3. The effects of different reaction parameters were studied and a biodiesel yield of 100% was obtained under the predicted optimum reaction conditions of methanol : oil molar ratio 15 : 1, catalyst amount 7 wt%, reaction temperature 55 °C and reaction time 2.5 h. The validation experiments showed a correlation coefficient of 0.95 between the predicted and experimental yield of biodiesel, which indicates the high significance of the model. The fuel properties of biodiesel obtained under the optimum conditions met the specifications as mentioned in ASTM D6751 and EN 14214 standards. Catalyst heterogeneity and low reaction temperature are the major attractions of the present biodiesel preparation strategy.