Abstract: In order to make hydroxytyrosol(HT) nano-liposomes stored at low temperature for a long time, the freeze-dried powder of HT nano-liposomes was prepared by freeze-drying method based on the preparation of the suspension of HT nano-liposomes. The freeze-drying process conditions were selected based on its appearance, redispersability, particle size and encapsulation rate as the main indexes, and the freeze-drying protective agent was screened by single factor test combined with orthogonal test to evaluate its stability. The results showed that the obtained freeze-dried powder was loose, smooth, flat and full appearance (appearance +++) when the freeze-dried protective agent was m (D-trehalose):m(sucrose): m(mannitol)=4:2:1 and the solution mass fraction was 10% at -50℃ for 8 h and freeze-drying for 72 h. The freeze-dried powder could redissolve into uniform suspension within 1 min of oscillation without soluble particles or clumps(redispersability +++), with water content of 3.28%±0.23%, the average particle size of(125.24±1.58) nm, and the encapsulation rate of 69.74%±0.94%. Transmission electron microscopy showed that the particles were round in appearance, smooth in surface and uniform in size. The stability study found that low temperature was more conducive to the stable storage of freeze-dried powder. When it was stored at 4℃ for 6 months, the freeze-dried powder exhibited better stability and no significant change in performance.