In this study, we found that AAEO significantly inhibited the migration and invasion of HepG2 and SMMC-7721 cells by downregulating the expression of DEPDC1. Moreover, in vivo metastasis assays confirmed that AAEO markedly inhibited the expression of DEPDC1 and reduced lung metastasis of HCC. The gene discussed is DEPDC1; the disease is hepatocellular carcinoma.