Cellular responses on a topographic surface are fundamental topics about interfaces and biology. Herein, a poly(lactide-co-glycolide) (PLGA) micropillar array was prepared and found to trigger significant self-deformation of cell nuclei. The time-dependent cell viability and thus cell proliferation was investigated. Despite significant nuclear deformation, all of the examined cell types (Hela, HepG2, MC3T3-E1, and NIH3T3) could survive and proliferate on the micropillar array yet exhibited different proliferation abilities. Compared to the corresponding groups on the smooth surface, the cell proliferation abilities on the micropillar array were decreased for Hela and MC3T3-E1 cells and did not change significantly for HepG2 and NIH3T3 cells. We also found that whether the proliferation ability changed was related to whether the nuclear sizes decreased in the micropillar array, and thus the size deformation of cell nuclei should, besides shape deformation, be taken into consideration in studies of cells on topological surfaces.