Multi-objective optimization of net energy, external costs of environment pollutant-emissions, and cost of using cassava-based fuel ethanol as an alternative automotive fuel in Guangxi has been conducted based on its holistic life cycle, from feedstock production to fuel combustion. A new indicator, cost of net energy (CNE), linking net energy-yield, external cost of environment pollutant-emissions, and production cost (the lower the CNE reading, the better the total performance) of ethanol-gasoline blends, is proposed for carrying out multi-objective optimization. On the life-cycle basis, CNE of ethanol-gasoline blends is found to obtain its lowest value, i.e. 0.119Â RMB/MJ, when processing fuel during the ethanol conversion stage was natural gas and the ratio of ethanol blended with gasoline was 5%. From the standpoint of the CNE indicator, the most viable implement form of cassava-based fuel ethanol should be used as one of oxygenate additives. The recommended processing fuel during ethanol conversion stage should be natural gas.