Cell wall disruption is an essential downstream processing step for improving the efficiency of lipid extraction from microalgae. Enzyme-assisted extraction of lipid from microalga Scenedesmus sp. with cellulase, xylanase and pectinase, using various parameters, such as enzyme concentration, temperature, pH and incubation time, was optimized by central composite design (CCD) coupled with response surface methodology (RSM). Both the lipid extraction from microalgae and the fatty acid methyl esters (FAMES) production under optimal conditions showed a twofold in the yields compared to the control group with no enzymatic treatment. SEM images, FTIR measurement, XPS and HPLC analysis showed that the enzymatic pretreatment caused significant alterations in the cell wall structure of microalgae. And the disruption of microalgal cell walls was primarily attributed to the breakage of beta-glucosidic linkages in cellulose and hemicellulose. The study showed a promising approach can lead to an improvement in the lipid extraction yield from microalgae and further provide valuable information for the use of enzymes in microalgal processes. (C) 2018 Published by Elsevier Ltd.