In this study, we successfully confirmed that, after exosomal ANXA2 derived from ovarian cancer uptaken by HMrSV5, ANXA2 protein can not only promote migration, invasion, apoptosis and MMT of HMrSV5 through downstream PI3K/AKT/mTOR pathway, but also accelerate the degradation of extracellular matrix, which provided pre‐metastatic niche for peritoneal invasion and metastasis of ovarian cancer. Here, ANXA2 is linked to ovarian cancer.