Nanomaterials have applications in environmental protection, hygiene, medicine, agriculture, and the food industry due to their enhanced bio-efficacy/toxicity as science and technology have progressed, notably nanotechnology. The extension in the use of nanoparticles in day-to-day products and their excellent efficacy raises worries about safety concerns associated with their use. Therefore, to understand their safety concerns and find the remedy, it is imperative to understand the rationales for their enhanced toxicity at low concentrations to minimize their potential side effects. The worldwide literature quotes different nanoparticle functions responsible for their enhanced bio-efficacy/ toxicity. Since the literature on the comparative toxicity study of nanoparticles of different shapes and sizes having different other physic-chemical properties like surface areas, surface charge, solubility, etc., evident that the nanoparticle's toxicity is not followed the fashion according to their shape, size, surface area, surface charge, solubility, and other Physico-chemical properties. It raises the question then what function of nanoparticle is the primary factor for their hyper toxicity. Why do non-spherical and large-sized nanoparticles show the same or higher toxicity to the same or different cell line or test organism instead of having lower surface area, surface charge, larger size, etc., than their corresponding spherical and smaller-sized nanoparticles? Are these factors a secondary, not primary, factor for nanoparticles hyper-toxicity? If so, what function of nanoparticles is the primary function for their hyper-toxicity? Therefore, in this article, literature related to the comparative toxicity of nanoparticles was thoroughly studied, and a hypothesis is put forth to address the aforesaid question, that the number of atoms/ions/ molecules per nanoparticles is the primary function of nanoparticles toxicity.