In this study, we report a role for EBV in promoting VM formation in NPC and gastric cancer cells through the PI3K/AKT/mTOR/HIF-1α axis and demonstrate a potential application of HIF-1α as a therapeutic target for EBV-associated epithelial cancers that are resistant to anti-VEGF therapy. Here, AKT1 is linked to nasopharyngeal carcinoma.