Effects of hydrophobic nano-SiO2 with different grain sizes and concentrations on CH4 hydrate formation were studied in this paper. Results showed that although the addition of hydrophobic nano-SiO2 did not change the phase equilibrium condition of CH4 hydrate, hydrate formation was promoted by enhancing the thermal conductivity of nano-fluid and increasing the gas-liquid contact area on the hydrophobic nano-SiO2 surface. When the grain size of hydrophobic nano-SiO2 was 80 nm and the concentration reached 5.0 wt%, there was no induction time for CH4 hydrate formation, and the average rate of CH4 hydrate formation increased 33.1% compared with ultrapure water experiment.