To extract the microalgal lipid in situ, biocompatible solvents were screened for lipid milking of Nannochloropsis sp. in an aqueous-organic system. The effects of organic solvents on the microalgal growth, the lipid extractability, the dehydrogenases activity and the cell membrane integrity were investigated by UV-visible spectrophotometer, FT-IR spectroscopy, 2,3,5-triphenyltetrazolium chloride (TTC) and Evans Blue stain method, respectively. The results showed that alkane solvents with log P > 5.5 were biocompatible while the hydrophilic solvents with log P < 5.5 were toxic to Nannochloropsis sp. due to the deactivated dehydrogenase and increased cell membrane permeability. As 10% (v/v) hexadecane was used to establish biphasic system, the total lipid production of Nannochloropsis sp. was increased by 28.9% compared to the control. The screened biocompatible solvent hexadecane enhanced not only the algal growth but also the lipid accumulation, showing an effective way to facilitate the process for in situ lipid milking from Nannochloropsis sp. (C) 2011 Elsevier Ltd. All rights reserved.