Hematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein (HPIP/PBXIP1) is a nucleo-cytoplasmic shuttling protein, and its expression is associated with cancer aggressiveness. However, the role of HPIP in ovarian cancer is still unclear. Here, we aimed to clarify the role of HPIP in epithelial-mesenchymal transition (EMT) process of ovarian cancer cells, stimulated by transforming growth factor (TGF)-β1. In this study, we found that HPIP was highly expressed in ovarian cancer cells, and TGF-β1 treatment induced HPIP expression in ovarian cancer cells. In addition, knockdown of HPIP suppressed TGF-β1-induced EMT and migration/invasion in ovarian cancer cells. Moreover, knockdown of HPIP significantly blocked the phosphorylated pattern of both PI3K and Akt induced by TGF-β1 in SKOV3 cells. In conclusion, the present study showed that HPIP silencing might prevent TGF-β1-induced EMT in ovarian cancer cells. Thus, HPIP may be a potential therapeutic target for the treatment of ovarian cancer.