Anyhow, we demonstrated that 5‐mg/kg of Anti‐PIEZO1‐MMAE could significantly suppress the tumor growth by inhibiting cell proliferation without any obvious damage to other normal organs and tissues, indicating that targeting PIEZO1 by conjugating its monoclonal antibody with MMAE is a quite feasible and efficient strategy to treat ESCC. Here, PIEZO1 is linked to esophageal squamous cell carcinoma.