Mixtures of a properly chosen oil (poly(dimethylsiloxane) (PDATS) or hydrocarbon) and hydrophobic particles (e.g., hydrophobized silica) have a strong deteriorating effect on foam stability, even when introduced in a very low concentration. These mixtures are widely used for foam control and are commonly termed antifoam compounds. In the present study, we check experimentally how the antifoam efficiency depends on the hydrophobicity of the solid particles. For this purpose, we prepare antifoam compounds by mixing silicone oil (PDMS) and hydrophilic silica at room temperature. The mild stirring of this mixture leads to a gradual PDMS adsorption on the silica surface, making it more hydrophobic. This process is very slow at room temperature and takes weeks before reaching the final, most hydrophobic state of the particles. Thus, we are able to check how the antifoam activity changes along the process of silica hydrophobization. Solutions of three surfactants (one ionic and two nonionic) are used as foaming media. In all of the studied systems, a well-pronounced maximum in the antifoam efficiency is observed at a certain optimal silica hydrophobicity, which depends on the used surfactant. The foam tests are complemented with several model experiments, and a plausible explanation of the observed phenomenon is suggested.