Wax esters are long-chain esters that have been widely applied in premium lubricants, parting agents, antifoaming agents and cosmetics. In this study, the biocatalytic preparation of a specific wax ester, cetyl octanoate, is performed in n-hexane using two commercial immobilized lipases, i.e., Lipozyme (R) RMIM (Rhizomucor miehei) and Novozym (R) 435 (Candida antarctica). Response surface methodology (RSM) and 5-level-4-factor central composite rotatable design (CCRD) are employed to evaluate the effects of reaction time (1-5 h), reaction temperature (45-65 degrees C), substrate molar ratio (1-3:1), and enzyme amount (10%-50%) on the yield of cetyl octanoate. Using RSM to optimize the reaction, the maximum yields reached 94% and 98% using Lipozyme (R) RMIM and Novozym (R) 435, respectively. The optimum conditions for synthesis of cetyl octanoate by both lipases are established and compared. Novozym (R) 435 proves to be a more efficient biocatalyst than Lipozyme (R) RMIM.