In conclusion, our findings suggested that HE4 knockdown mediates the reduced cell proliferation, invasion, migration and tumor growth as well as increased apoptosis through inactivation of the JAK/STAT3 pathway, which provides us a better understanding the function and mechanisms of HE4 in malignant progression of ovarian cancer and might promote to develop a new therapeutic and promising option for patients with ovarian cancer. This evidence concerns the gene WFDC2 and ovarian cancer.