Thus, due to the potential roles of miR-125 and E in regulating mitochondrial dynamics, apoptosis, and migration of cancer cells, we aimed to explore the effects and mechanisms of the combinatorial therapy of miR-125/SLN-KL and E/LPN-KL in suppressing HNC via multiple signaling modulations of tumor energy metabolism, metastasis, and resistance in vitro and in vivo. The gene discussed is KL; the disease is cancer.