In the present study, we observed that 17β‐estradiol treatment significantly inhibited HBMMSCS‐mediated cell motility activity through suppressing IL‐8‐Src downstream target protein activation and expression, including Cas, paxillin, ERK1/2, JNK1/2, MMP9, tPA and uPA in human gastric cancer cells. The gene discussed is PXN; the disease is gastric cancer.