Clinical studies of circulating tumor cells (CTC) have stringent demands for high capture purity and high capture efficiency. Nanostructured surfaces have been shown to significantly increase the capture efficiency yet suffer from low capture purity. Here we introduce a dual-functional lipid coating on nanostructured surfaces. The lipid coating serves both as an effective passivation layer that helps prevent nonspecific cell adhesion and as a functionalized layer for antibody-based specific cell capture. In addition, the fluidity of lipid bilayers enables antibody clustering that enhances the cell-surface interaction for efficient cell capture. As a result, the lipid-coating method helps promote both the capture efficiency and capture purity of nanostructure-based CTC capture.