Mesoporous Silica Nanoparticles (MSNs) have received increasing attention in biomedical applications due to their tuneable pore size, surface area, size, surface chemistry, and thermal stability. The biocompatibility of MSNs, although generally believed to be satisfactory, is unclear. Physicochemical properties of MSNs, such as diameter size, morphology, and surface charge, control their biological interactions and toxicity. Experimental conditions also play an essential role in influencing toxicological results. Therefore, the present study includes studies from the last five years to statistically analyse the effect of various physicochemical features on MSN-induced in-vitro cytotoxicity profiles. Due to non-normally distributed data and the presence of outliers, a Kruskal–Wallis H test was conducted on different physicochemical characteristics, including diameter sizes, zeta-potential measurements, and functionalisation of MSNs, based on the viability results, and statistical differences were obtained. Subsequently, pairwise comparisons were performed using Dunn’s procedure with a Bonferroni correction for multiple comparisons. Other experimental parameters, such as type of cell line used, cell viability measurement assay, and incubation time, were also explored and analysed for statistically significant results.