Metastasis is the leading cause of death in nasopharyngeal carcinoma (NPC), with its precise mechanism still unclear. Here we constructed high metastatic (HM) and low metastatic (LM) sublines of NPC cells via the Transwell system to research the metabolic alterations that occur during NPC metastasis. The results of metabolomics and proteomics propose that under the metabolic stress, enhanced UDP-GlcNAc promotes the O-GlcNAc modification of PRRC2C, which is a marker of Stress granules (SGs), and favor SG formation. Meanwhile, the enrichment of SG lead to alterations in mitochondrial dynamics. Mechanistically, the SG core protein NUFIP2 supressed the mTOR activity and enhanced lipophagy, as a result, reduced mitochondrial lipotoxicity and enhanced mitochondrial fission were observed in HM cells to maintain mitochondrial homeostasis. In the nude mice in situ transfer model, the use of EGCG could revise the metastatic potential of HM cells via the inhibition of SGs, thereby providing a feasible treatment strategy for patients with metastatic NPC.