The present study’s results represent a significant advancement in understanding the modulation of ER−mitochondrial bioenergetics by the MCPIP1-modulated let-7g–KRAS–PI3K–Rac1–Akt signaling axis and provide a mechanistic explanation for the role of KRAS as a crucial regulator of metabolic reprogramming towards the coordination of aerobic glycolysis and mitochondrial OXPHOS in the energy generation of NPC cells. This evidence concerns the gene RAC1 and nasopharyngeal carcinoma.