A method for the prediction of isobutane solubility in H2SO4 was developed based on the COSMO-RS model and applied to predict the isobutane solubilities and isobutane–olefin ratios (I/O) in (H2SO4 + additives) and [H2SO4 + ASO (acid-soluble oil) compounds]. The results were used to investigate the mechanisms by which the additives increase the C8 selectivity of the isobutane alkylation. The principal finding is that all the additives considered enhance the C8 selectivity by increasing the I/O value, rather than the isobutane solubility, which presents a challenge to the common belief that the additives promote the C8 selectivity by increasing the isobutane solubility in H2SO4. Typical ASO monocyclic compounds increase the isobutane solubility and the I/O value in the acid phase, indicating that these compounds can enhance the performance of the H2SO4 catalyst. The results can be used to optimize the isobutane alkylation process and to design and develop innovative additives for the isobutane alkylation.