Cyano-functionalized spherical silica nanoparticles (SNPs) were synthesized via Stober method. A 2(IV)(k-p)-fractional factorial design (2k-(k-p)(IV)-FFD) was used to smartly prepare monodispersed evenly distributed SNPs. Six factors were considered; concentrations of tetraethylorthosilicate (TEOS), 3-Cyanopropyltriethoxysilane (CPTS), water, and ammonia, reaction time (RT) and stirring time (ST). Two responses; particle size (PS, measured by SEM) and particle-size distribution (PSD, calculated as standard deviation, +/- SD) were measured. Control charts were used to decide on impacts of linear and two-way interactions on both responses. Derringer's function was used to consolidate these multifarious responses into a uniform execution characteristic. Both screening and optimization were always accompanied by ANOVA testing at a 95.0% confidence interval (CI). The ideal synthetic conditions were obtained from the composite desirability plots. Cyano-functionalized SNPs with an average PS of 474.04 +/- 86.71 nm were produced. Raman spectroscopy and FTIR were used to confirm the functionalization process. Thermogravimetric analysis (TGA) was used to evaluate the thermal behavior of synthesized particles. (C) 2018 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.