While various cellular responses to materials have been published, little concerns the deformation of cell nuclei. Herein we fabricated a polymeric micropillar array of appropriate dimensions to trigger the significant self-deformation of cell nuclei and examined six cell types, which could be classified into cancerous cells (Hela and HepG2) versus healthy cells (HCvEpC, MC3T3-E1, NIH3T3, and hMSC) or epithelial-like cells (Hela, HepG2, and HCvEpC) versus fibroblast-like cells (MC3T3-E1, NIH3T3, and hMSC). While all of the cell types exhibited severe nuclear deformation on the poly(lactide- co-glycolide) (PLGA) micropillar array, the difference between the epithelial-like and fibroblast-like cells was much more significant than that between the cancerous and healthy cells. We also examined the statistics of nuclear shape indexes of cells with an inevitable dispersity of nuclear sizes. It was found that larger nuclei favored more significant deformation on the micropillar array for each cell type. In the same region of nuclear size, the parts of the epithelial-like cells exhibited more significant nuclear deformation than those of the fibroblast-like cells. Hence, this article reports the nuclear size dependence of the self-deformation of cell nuclei on micropillar arrays for the first time and meanwhile strengthens the cell-type dependence.