A systematic approach involving factor grouping, factorial design and response surface analysis was demonstrated to be an effective method for studying the effects of a large number of nutrients on cell growth and lipid production of the green alga Neochloris oleoabundans for the purpose of medium optimisation. Box-Behnken experimental design (BBD) was used for factorial experimental design and response surface method (RSM) was used for data analysis. The optimised medium obtained was able to support a lipid yield of 641.4mglipid/L and a cell density of 2.54 g/L, which were 4.5- and 2.2-fold of that obtained with the basic medium, modified Bristol medium (MBM), respectively.