To improve the water solubility of glaucocalyxin A (GLA) by the preparation of glaucocalyxin A γ-cyclodextrin clathrate (GLA-γ-CD) and to investigate the inhibitory effect of GLA-γ-CD on tumor growth in S180 cell xenografts.GLA-γ-CD, γ-cyclodextrin (γ-CD) and GLA were combined at a mass ratio of 1:1, dissolved in 60°C water by stirring. GLA completely entrapped by the γ-CD was verified by differential thermal analysis, the GLA content was determined. Phase solubility, solubility, and in vitro dissolution rate experiments were performed. The S180 xenograft mouse model was used to observe the tumor inhibitory effects of GLA-γ-CD and GLA, and the TUNEL assay was used to detect differences in their rates of tumor cell apoptosis induction.After combination with γ-CD, the solubility of GLA-γ-CD was 21.78-fold greater than that of GLA. The in vitro dissolution rate of GLA-γ-CD was significantly greater than that of GLA, and reached more than 90% in 20 min. Furthermore, GLA-γ-CD was more effective than GLA as an inhibitor of S180 tumor cells; the inhibitory rate of the high-dose group reached 57.26%, which was 54.11% greater than the inhibitory rate of the GLA group at the same dose. In addition, GLA-γ-CD induced tumor cell apoptosis more effectively than did GLA.The water solubility of GLA significantly increased in combination with γ-CD resulting in the production of GLA-γ-CD. Furthermore, GLA-γ-CD was more effective than GLA as an inducer of S180 tumor cell apoptosis and an inhibitor of tumor growth.