Compared with the control group, after 24h of geniposide action, the expression of the PTEN, Bax, and Caspase-3 proteins in HSC-3 cells increased significantly, and the expression of the p-EGFR, p-AKT, and Bcl-2 proteins decreased significantly, indicating that geniposide may inhibit oral squamous cell carcinoma through multi-target regulation of the PI3K-Akt signaling pathway. This evidence concerns the gene PTEN and oral cavity squamous cell carcinoma.