These findings uncover that Drp1 overexpression drived the growth and metastasis of ESCC via ROS-PGC1-α-Nrf1/2 signaling pathway, while miR-203a-3p significantly inhibited Drp1 expression and its capacity to mediate the malignant progression of ESCC cells. The gene discussed is PPARGC1A; the disease is esophageal squamous cell carcinoma.