Epithelial ovarian cancer ranks as the 5th most deadly female cancer. However, few effective biomarkers have been identified for clinical application. Thus, it is critical to identify differentially expressed genes in epithelial ovarian cancer patient samples. Our work has focused on a tumor suppressor gene Neurofibromin 1 and its role in epithelial ovarian cancer pathology. We examined 124 samples of benign ovarian tissues, borderline ovarian tissues, and epithelial ovarian cancer tissues for NF1 expression by immunohistochemistry and further validated our results using RT-PCR and Western blot. We next analyzed the follow-up information with pathological features using Kaplan-Meier univariate survival analysis and Cox regression multivariate analysis. First, our results show that the mRNA level and protein level of NF1 are significantly decreased in epithelial ovarian cancer patients. Second, NF1 expression is negatively associated with 5-year overall survival, lymph node metastasis, and tumor size. Furthermore, our data also suggests that NF1 expression is a protective factor for epithelial ovarian cancer prognosis. NF1 is negatively regulated in EOC patients and low expression of NF1 is associated with lymph node metastasis. More importantly, patients that have lost NF1 showed poorer prognosis and five-year overall survival.