ERK1-OE Lentivirus reversed the decreased p-ERK1/2, MMP2 and MMP9 in ECA109 cells, indicating that the miR-181a-5p elevation suppressed the activation of the ERK1/2-induced MMP2/9 pathway in ESCC through MEK1 gene. Here, MMP2 is linked to esophageal squamous cell carcinoma.