In this study, we identified HSP90A as an important target of (20S) G-Rh2 in liver cancer cells, and for the first time, we elucidated the anti-tumor mechanism of (20S) G-Rh2 inducing G1 phase arrest by targeting and disrupting the HSP90A-Cdc37 system. This evidence concerns the gene HSP90AA1 and liver cancer.