Meningioma-associated protein (MAC30), first described to be overexpressed in meningiomas, exhibits altered expression in certain human tumors. The definite role of MAC30 is not clear now, and few studies have documented the value of MAC30 in epithelial ovarian cancer (EOC). The aim of this study was to investigate the expression of MAC30 in EOC and to evaluate its clinical significance in patients with EOC. A total of 266 patients with EOC who undergone complete cytoreductive surgery from November 2003 to September 2006 were eligible for this study. The expression of MAC30 in epithelial ovarian tumor tissues was examined immunohistochemically. High expression of MAC30 was observed in 66.17 % of EOC. The high MAC30 expression group had more advanced stages, poorer histological grade, lymph node metastasis, and recurrence than those with low MAC30 expression. Moreover, the presence of lymph node metastasis was significantly associated with MAC30 expression (OR 2.888, 95 % CI 1.428-5.838, P = 0.003). In addition, it was also shown that high MAC30 expression significantly correlated with poorer overall survival and progression-free survival (both P < 0.001). Multivariate Cox regression analysis revealed that MAC30 expression status was an independent prognostic factor for both overall survival and progression-free survival (P = 0.001 and P = 0.002, respectively) of patients with EOC. Our study provides evidence that patients with expression of MAC30 in EOC have high malignant potential, and MAC30 may serve as a new molecular marker to predict the lymph node metastasis and prognosis of patients with EOC in the clinic.