The application of nanoparticles to freeze-drying of cells was studied. In the present study, the effect of different mass concentrations of hydroxyapatite nanoparticles (0, 0.1, 0.3, 0.5, 0.7, 1,5 g/L) into lyoprotectant on freeze-drying of HepG2 cells was investigated. When the concentration of HA nanoparticles is 0.5 g/L, the freeze-drying effect of cells is the best. The recovery rate and survival rate after rehydration of freeze-drying HepG2 cells reach 37.39% and 62.06% (P<0.05) respectively. Meanwhile, when the concentration of HA nanoparticles is over 0.5 g/L, the 24 h adherence rate of cells decreases significantly. The results suggest that the addition of appropriate concentration of HA nanoparticles can improve the outcome of freeze-drying of cells, while the high level of HA nanoparticles may damage cells during freeze-drying. The addition of HA nanoparticles into lyoprotectant is effective to preserve cells during freezing and subliming processes, and is not effective during thawing process.