The study aimed to investigate the effects and possible mechanisms of oridonin (ORI) on the proliferation, invasion and migration of SKM-1 cells. SKM-1 cells were divided into normal control (NC) group, ORI group, miR-NC group, miR-125a group, ORI+miR-NC group and ORI+miR-125a group. The ability of cell proliferation was evaluated by CCK-8 method. Transwell assay was used to detect the migration and invasion ability. Real time PCR was used to detect the expression level of miR-125a in cells. The protein levels related to protein kinase B (AKT)/forkhead box O3a (FOXO3a)/B cell lymphoma-2 interacting mediator of cell death (BIM) signaling pathway were analyzed by Western blot. The results showed that ORI could inhibit the proliferation rate of SKM-1 cells. Compared with NC group, the number of cell invasion and migration in ORI group was decreased, while the mRNA expression level of miR-125a also was decreased, while the apoptosis rate was increased. In addition, compared with NC group or miR-NC group, the cell proliferation ability of miR-125a group was enhanced, and the number of cell invasion and migration cells was increased, and the apoptosis rate was significantly decreased. However, compared with ORI group and ORI+miR-NC group, the number of invasion and migration in ORI+miR-NC group was increased, but the apoptosis rate was significantly increased. Compared with the NC group, the protein levels of phosphorylated AKT (p-AKT) and phosphorylated FOXO3a (p-FOXO3a) in the ORI group were significantly reduced, while the protein levels of FOXO3a and BIM were significantly decreased. In contrast, compared with the ORI+miR-NC group, the protein levels of p-AKT and p-FOXO3a in the ORI+miR-125a group were significantly increased, while the protein levels of FOXO3a and BIM were significantly decreased. In conclusion, ORI can down regulate miR-125a, modulate AKT/FOXO3a/BIM signaling pathway, and then inhibit the proliferation, invasion and migration of SKM-1 cells.