Our study found that ECSCs had increased p-ERK1/2 activity compared with normal esophageal cancer cells, and blockage of CXCL12 or CXCR4 could significantly inhibit the activity of p-ERK1/2, while adding rhCXCL12 could significantly enhance the activity of p-ERK1/2, therefore confirming that ECSCs maintained high activity of p-ERK1/2 by the CXCL12-CXCR4 chemokine axis. The gene discussed is MAPK3; the disease is esophageal cancer.