Ovarian cancer is recognized as one of the worst gynecologic malignancies associated with rapid metastasis and poor overall survival rate. The identified valuable molecular biomarkers criticize importance of timely diagnosis for ovarian cancer. Salusin-β levels are dramatically increased in women with polycystic ovarian syndrome. However, the roles of salusin-β in ovarian cancer have yet to be fully elucidated. A total of 57 paired ovarian cancer specimens and matched adjacent normal tissues were used to measure the salusin-β levels. The prognostic value of salusin-β for tumor progression and survival rate was investigated. The effects of salusin-β on ovarian cancer cell proliferation and epithelial-mesenchymal transition were also explored. The expression of salusin-β was significantly increased in ovarian cancer tissue specimens compared with matched normal adjacent tissue (P<0.05). The high salusin-β level was closely related with FIGO stage and lymph node metastases. The ovarian cancer patients with high salusin-β had a shorter overall survival (P<0.05). Salusin-β obviously enhanced the proliferation and epithelial mesenchymal-transition of SKOV3 cells. Furthermore, salusin-β substantially decreased the expression of p-GSK-3β and GSK-3β, but stimulated the β-catenin expression and downstream genes of wnt/β-catenin including cyclin D1 and C-myc. Our data demonstrated for the first time that upregulated salusin-β may be a novel independent prognostic biomarker for overall survival of ovarian cancer. Salusin-β accelerated the proliferation and epithelial mesenchymal transition of ovarian cancer cells at least partly via activation of Wnt/β-catenin signaling pathway. Salusin-β may be an important target for therapeutic intervention in ovarian cancer.