Introduction/objective: Ovarian cancer is the 6th leading cause of mortality in women, killing more women than any other reproductive system cancer. We studied the expression of serum micro-ribonucleic acid-21 (miRNA-21) in ovarian cancer patients and explored associations with diagnosis, clinicopathological parameters, and prognosis. Methods: Real-time fluorescence-quantitative polymerase chain reaction was used to examine the relative expression of miRNA-21 in serum. Cancer antigen 125 (CA-125) levels were measured using an enzyme immunoassay test kit (ELISA). Results: Serum miR-21 expression was significantly elevated in ovarian cancer patients compared to controls (p < 0.001). The same was true for CA-125 serum levels, which were also significantly in cancer patients (p < 0.001). The sensitivity and specificity of miR-21 detection in the diagnosis of ovarian cancer were 96%, 88% versus 74%, and 80% for CA-125. Conclusions: miR-21 is highly expressed in the serum of ovarian cancer patients and may be important in the development and progression of ovarian cancer, with more sensitivity and specificity than CA-125. Our results suggest that circulating serum miRNA-21 is a promising tumor marker for use in the diagnosis and prognosis of ovarian cancer.