Squalene is a linear triterpenoid with six non-conjugated double bonds. Its physiological function is remarkable, but its application is limited due to its poor water solubility and stability. The interactions between squalene and different cyclodextrins, including α-cyclodextrin,β-cyclodextrin,γ-cyclodextrin,hydroxypropyl-β-cyclodextrin and methyl-β-cyclodextrin were studied by phase solubility method at different temperatures(25, 40 and 55 ℃). The phase dissolution diagrams were plotted and the thermodynamic parameters during the inclusion process were calculated. The results showed that all phase dissolving diagrams were AL type. The inclusion effect and solubilization effect of γ-cyclodextrin were the most remarkable. The inclusion constant K of γ-cyclodextrin for squalene was up to 1778.0860 L/mol, and the solubility of squalene increased to 309.0935 times. The thermodynamic parameters enthalpy change(ΔH) and entropy change(ΔS) of the inclusion process were both positive values, while Gibbs free energy(ΔG) were both negative values, indicating that the inclusion process was an endothermic spontaneous reaction, and the increase of disorder(entropy increase) was the main driving force for the encapsulation of squalene molecules in cyclodextrin cavities.