Nanoparticle technology has recently emerged as a potential solution for a number of challenges facing the oil industry. Because of their unique features and special properties, nanoparticles could be used as adsorbents and catalysts for enhancing heavy oil quality. Our research group has used nanoparticle technology to integrate carbon rejection with hydrogen addition processes. Hence, nanoparticles could be used as adsorbents to remove heavy polar hydrocarbons from heavy oil and subsequently be used as catalysts for post-adsorption decomposition of the adsorbed heavy hydrocarbons. In continuation of previous work on using nanoparticles as adsorbents and catalysts for heavy polar hydrocarbons, in this study we explore size effects of NiO nanoparticles on their adsorptive and catalytic properties towards heavy hydrocarbons, exemplified by Quinolin-65 (Q-65). Therefore, the purposes of this study include: (1) preparing and characterizing different sizes of NiO nanoparticles; and (2) comparing the adsorptive and catalytic performances of the prepared different sizes of nanoparticles for the adsorption Q-65 from toluene and post-adsorption oxidation of adsorbed Q-65. Accordingly, adsorption isotherms are described by solid-liquid equilibrium (SLE) model, and the catalytic behavior of the nanoparticles are compared on the basis of the effective activation energies trends using the isoconversional method. Side by side, computational modeling is conducted to understand the chemistry behind the differences of adsorption capacity and catalytic activity of the different sizes of NiO nanoparticles. An optimum nanosize of NiO nanoparticles is established which a higher adsorption capacity and minimum activation energy are obtained. These findings open up new possibilities for employing adsorptive and catalytic profiles of metal oxide nanoparticles, and extend our general understanding of their surface functionality and chemical activity. Moreover, this study gives a good chance to go through real crude oil to be investigated by different nanosize adsorbents as a continuing work.