Foam plugging performance was of great significance for improving oil recovery in reservoir development. In view of the agglomeration phenomenon of SiO2, molecular dynamics simulation was used to verify whether hydrophilic or hydrophobic modification had better dispersion effect on nanoparticles. The effect of SiO2 dispersion was verified by establishing gas–liquid interface model based on molecular dynamics. Meanwhile, SiO2 nanoparticles were modified and the best modification effect was characterized compared with the first modification and the second modification. The dispersion effect of SiO2 nanoparticles was researched by measuring the particle size, observing the morphology by the TEM test and measuring the specific surface area. The foam performance stabilized by SiO2 was evaluated in terms of single factor and multi-factor experimental design through RSM/CCD. According to the result analysis, the modification effect represented hydrophilic was more suitable considering dispersion. Good dispersion of SiO2 nanoparticles was beneficial to slow the decay of foam dispersions and limit the diffusion of water molecules due to interfacial interaction. The effects of second modification were more hydrophilic than the first through FT-IR and TGA. The interfacial tension test showed that the hydrophilic foam dispersion had better foam stability. The optimum foaming condition for single factor was respectively achieved at hydrophilic SiO2 1.5 wt.%, the pH values with 7 and the temperature of 30 °C. The optimum conditions of the foaming volume for multi-factors were 1.506 wt.% hydrophilic SiO2, pH of 8.220 and 31.306 °C, respectively. The best conditions for the half-life were presented to be 1.352 wt.% hydrophilic SiO2, the pH of 7.884 and 26.139 °C, respectively. The maximum foam volume and foam half-life predicted by design 10.0 were 750.241 mL and 358.474 min. Therefore, it was significant to modify the surface of SiO2 nanoparticles (5–25 μm) for improving the dispersion and strengthening the foam stability in high permeability reservoir.