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 clathration of squalene with alpha-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin, hydroxypropyl-beta-cyclodextrin and methyl-beta-cyclodextrin were studied by phase solubility method at temperatures of 25℃, 40℃ and 55℃. While the phase dissolution diagrams were plotted and the thermodynamic parameters during the inclusion process were calculated. The results showed that all the phase dissolving diagrams were AL type, and the inclusion effect and solubilization effect of gamma-cyclodextrin were the most significant. The inclusion constant K of gamma-cyclodextrin for squalene was up to 1778.0860 L/mol, and the solubility of squalene was increased to 309.0935 times. The thermodynamic parameters enthalpy change (ΔH) and entropy change (ΔS) of the inclusion process are both positive values, while the Gibbs free energy (ΔG) are both negative values, indicated that the inclusion process is an endothermic spontaneous reaction, and the increase of disorder (entropy increase) is the main driving force for the encapsulation of squalene molecules in cyclodextrin cavities.