In conclusion, this study confirmed for the first time that CD147 and HE4 protein could interact with each other and were both associated with the poor prognosis of ovarian cancer, and HE4 can promote the invasion and metastasis of ovarian cancer by regulating the expression of CD147, ANXA2 may play a “bridge” role in this process, which provides a theoretical basis for the further study of underlying mechanism of CD147 and HE4 interaction in ovarian cancer. Here, WFDC2 is linked to ovarian cancer.