Abstract: Hesperidin nanosuspensions (HDN-NS) were prepared with tea saponin (TS) as stabilizer. The feasibility of TS as a natural stabilizer and the mechanism of TS stabilized nanosuspensions were investigated to provide reference for the development of green nano-preparations of hesperidin. HDN-NS was prepared by high-speed shearing combined with high-pressure homogenization. Using average particle size and polydispersity index as evaluation indexes, the effects of drug concentration, shearing speed, shearing time, homogeneous pressure and homogeneous cycles on HDN-NS were investigated by single factor experiment. The results of single factor investigation were as follows: drug concentration was 8.0 mg·mL^-1, shearing speed was 16 000 r·min^-1, shearing time was 2 min, the homogeneous cycles were 6 cycles at 35 MPa and 12 cycles at 100 MPa. The pH, ionic strength, zeta potential and critical micelle concentration of TS were investigated to determine the role of electrostatic repulsion in the mechanism of TS stabilized nanosuspensions. The results showed that electrostatic repulsion is involved in the mechanism of TS stabilized HDN-NS. In conclusion, at low concentration, TS can significantly reduce the particle size of HDN-NS, which indicates that TS has the potential to stabilize nanosuspension. Electrostatic repulsion is one of the mechanisms of TS stabilizing nanosuspension.