Intensive studies with vertical nanowire (NW) arrays have illustrated broad implications for manipulating mammalian cells in vitro, but how cellular responses are influenced by the presence of NWs has not been thoroughly investigated. Here, we address collective cellular behaviors, including surface area of cells, membrane trafficking, focal adhesion distribution and dynamics, and cytoskeletal protein distribution on amine-coated silicon (Si) NWs with different physical properties. The degree of HeLa cell spreading was inversely proportional to the surface area occupied by the NWs, which was not affected by manipulation of membrane trafficking dynamics. In the presence of a diffusive focal complex around the NWs, strong, well organized focal adhesion was hardly visible on the NWs, implying that the cells were interacting weakly with the NW-embedded surface. Furthermore, we found that actin filament formation of the cells on long NWs was not favorable, and this could explain our observation of reduced cell spreading, as well as the decreased number of focal adhesion complexes. Taken together, our results suggest that cells can survive on silicon NWs by adjusting their morphology and adhesion behavior through actively organizing these molecules.