By performing a series of experiments, we revealed that over‐expression of LRP6 or inhibition of miR‐590 partly reversed the inhibition roles of ESCCAL‐1 silencing in cell proliferation, invasion, and metastasis; more importantly, a similar trend also was observed in EMT related protein expression; strongly demonstrating that ESCCAL‐1 promoted ESCC progression mediated modulation miR‐590/LRP6. The gene discussed is LRP6; the disease is esophageal squamous cell carcinoma.