Mechanochemical (MC) processes are often modified to a large extent with use of process control agents (PCAs). An appropriate PCA is, however, chosen semi-empirically for any MC process such as ball-milling. In this study, milling period and medium, PCA kinds and amount, and powder kinds, are altered as major parameters to systematically and mechanistically investigate the effect of PCAs on powder milling and the related phenomena. The model systems selected are TiO2and ZnO powders with various PCAs including alkanes, alcohols, water, and a few ionic liquids. According to X-ray line broadening analyses the viscosity and the structure of PCA molecules strongly affect the MC process. In addition, the MC process for harder TiO2is quite different from ZnO, and oxygen-derived polarity of PCA molecules would cause major difference on the milling behavior. Various parameters controlling the MC process will be discussed.