The effects and mechanisms of cantharidin (CTD), a pharmacological component of Mongolian medicine Alaga Banbu, on the proliferation, invasion, and migration of human hepatocellular carcinoma were studied. Human liver cancer cell lines HepG-2 and SMMC-7721 were used as the research subjects. In the first part of the experiment, the groups were divided into high, medium, and low concentration CTD groups. In the second part, the groups were divided into Control, CTD, PI3K inhibitor LY294002, and CTD+LY294002 groups. The effects on cell proliferation, migration, and invasion were assessed using CCK-8, wound healing, and invasion assays. Western Blot analysis was performed to examine the expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), phosphatidylinositol-3-kinase(PI3K), phosphorylated phosphatidylinositol-3-kinase (p-PI3K), protein kinase B (Akt), and phosphorylated protein kinase B (p-Akt). The results show that CTD inhibits the proliferation, migration, and invasion of human liver cancer cells in a concentration-dependent manner, with statistically significant differences (P<0.05). After CTD treatment of HepG-2 cells, the protein expression of MMP-9 and MMP-2 is downregulated, and the differences are significant (P<0.05). Compared to the control group, all experimental groups inhibit the proliferation, invasion, and migration of human liver cancer cells. The combined drug treatment group show a more significant inhibitory effect than the same concentration of single drug treatment, with statistically significant differences (P<0.05). After treatment with each experimental group, the expression of p-PI3K, p-Akt, MMP-9, and MMP-2 was downregulated in HepG-2 cells, and the differences were significant (P<0.05). The combined drug treatment group showed the most significant protein expression differences compared to the single drug treatment group at the same concentration (P<0.05). The active ingredient Cantharidin from Mongolian medicine Araga-Banbu shares a common mechanism of action with the PI3K inhibitor. It is hypothesized that Cantharidin inhibits cell invasion and migration via the PI3K/Akt signaling pathway.