Human MOF (hMOF) is a major acetylase of human H4K16 involved in the regulation of physiological and pathological processes. We investigated the expression of hMOF in different ovarian tissues and its correlation with ovarian cancer prognosis. Reverse transcription PCR and western blot analysis were used to detect hMOF mRNA and protein expression, respectively, in different ovarian tissues. Immunohistochemistry was also performed to detect hMOF expression in different ovarian tissues, including ovarian epithelial cancer, borderline tumor, benign tumor and normal ovarian tissues. In addition, the relationships between hMOF expression and clinicopathological ovarian cancer data were analyzed. The Cox proportional-hazards regression model was used to analyze the factors associated with ovarian cancer prognosis. To analyze the effects of hMOF expression on ovarian cancer prognosis, a survival curve was plotted from the follow-up data of 77 patients with ovarian cancer. Compared with normal ovarian tissues, hMOF mRNA and protein expression was significantly decreased in ovarian epithelial cancer tissues. The proportions of high hMOF expression in normal and benign ovarian epithelial tumor tissues, were much higher than those in ovarian epithelial cancer tissues. Furthermore, hMOF protein expression was closely associated with the ovarian cancer stage. The expression of hMOF protein was determined as an independent risk factor influencing ovarian cancer prognosis. Patients with high hMOF levels showed improved survival than those with low hMOF levels. hMOF mRNA and protein expression decreased in ovarian epithelial cancer, thus the hMOF protein potentially serves as a new clinical marker of ovarian cancer prognosis.