The SiO2 synthesized in bulk form, adopting the conventional methods for application in food industry applications, may also contain nano-sized particles. On account of the unique physico-chemical properties, the SiO2 particulates, such as size and shape, cause metabolic toxicity in cells. Poor understanding of the molecular level nanotoxicity resulting from high-volume synthetic SiO2 exposures in humans is a serious issue, since these particles may also contribute to metabolic stress-mediated chronic diseases. In the present study, we examined the structural characteristics of these nano-sized silica particles adopting SEM and dynamic light scattering (DLS) and assessed the alterations in the cell cycle induced by these silica particles in human mesenchymal stem cells (hMSCs) adopting 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay, morphological changes in the cells adopting fluorescent microscopy, cell cycle analysis adopting flow cytometry, and the expression of genes linked to cell cycle (i.e., proliferating cell nuclear antigen (PCNA), early growth response protein (EGR1), E2F transcription factor (E2F1), cyclin D1, cyclin C, and cyclin D3) adopting qPCR. The SEM and DLS studies indicated that the commercial grade SiO2-NPs were in the nano-scale range. Alterations in the cytoplasmic organization, nuclear morphology, cell cycle progression, and expression of genes linked to cell cycle-dependent metabolic stress through EGR1, CCND, and E2F1 genes were the primary indicators of metabolic stress. Overall, the results of this study demonstrate that synthetic SiO2 acutely affects hMSC through cell cycle-dependent oxidative stress gene network. The toxicity mechanisms (both acute and chronic) of food grade silica should be investigated in greater depth with special reference to food safety.