Transesterification of non-natural trimethylsilyl alcohol with fatty ester in organic phase could be catalyzed by lipase from Candida cylindracea. The transesterification reaction was apparently affected by the hydrophobicity of reaction medium, the water activity of the reaction system and the structure of the substrates. n-Octane was found to be the best medium for the reaction and the optimum water activity for the reaction is about 0.55.