This is an article describing a novel technology where hydrophobic nanoparticle acts as a foam controller to facilitate protein separation. Valuable sweet potato protein (SPP), a protein model, mainly exits in sweet potato starch wastewater (SPSW), and its separation is desperately needed to enable a sustainable utilization of waste and reduce the environmental burden. We firstly used hydrophobic silica nanoparticle (SNP) in situ modified by dodecyl dimethyl betaine (BS12) as a foam stabilizer instead of surfactants to improve SPSW foam stability. Somewhat unexpectedly, the particle also intensified the interfacial adsorption of SPP. Subsequently, a foam separation column with a vertical ellipsoid-shaped channel (VEC) was proposed to gently strengthen foam drainage and then enhance the enrichment ratio of SPP (E-SPP). Most importantly, the negative impact of VEC on the recovery percentage of SPP (R-SPP) was found to be negligible in the presence of modified SNP because it maintained the film thickness. After the foam separation, unmodified SNP served as a defoamer to accelerate bubble breakage. Eventually, R-SPP and E-SPP reached 80.6 +/- 4.0% and 9.1 +/- 0.5, respectively, using the SNP as a foam controller. We expect this technology to be a complementary and/or alternative strategy for protein separation.