Silica nanoparticles are being formulated for potential drug delivery and for imaging and diagnostic applications in the central nervous system (CNS). However, the potential and underlying mechanism of silica nanoparticles-mediated neurotoxicity has remained unclear. We examined the effect of colloidal silica nanoparticle (LUDOX$^{(R)}$ TM) on neurite outgrowth and neurotoxicity of human SH-SY5Y neuroblastoma cells differentiated by all-$trans$-retinoic acid (RA). Exposure of >300 ppm of $SiO_2$ TM nanoparticle in differentiating cells showed less cytotoxicity than in undifferentiated cells. 100 ppm of $SiO_2$ TM nanoparticle had no significant difference on the viability of either undifferentiated or differentiating SH-SY5Y cells. Neurite outgrowth in differentiating cells for 48 h exposure of 100 ppm $SiO_2$ TM nanoparticle was not significantly changed. Thus, $SiO_2$ TM nanoparticle appeared no effects in the early initiation of neurites. And also, although the production of reactive oxygen species (ROS) was not induced, neurotoxicity resulted by $SiO_2$ TM nanoparticle may be the result of increased DNA damage, apoptosis, and cell cycle arrest in undifferentiated and differentiating cells. Further studies are needed to investigate the expression of genes in these signaling pathways in response to exposure to silica nanoparticle and to investigate the molecular mechanisms of neuronal cell effects.