Objective: To investigate the diagnostic value of combined use of serum CA125 and plasma D-dimer in ovarian cancer. Methods: Totally 109 patients with ovarian tumor were randomly selected. According to the result of pathology examination, patients were divided into two groups, benign ovarian tumor group (59 cases) and malignant ovarian tumor group (50 cases). Thirty healthy subjects were also selected as control group during the same period. The level of serum CA125 and plasma D-dimer was measured. Results: Combined use of serum CA125 and plasma D-dimer can improve the diagnostic accuracy of ovarian malignant tumors. The level of plasma D-dimer in advanced malignant ovarian tumor patients was significantly higher than that of patients with early malignant ovarian tumor. The level of plasma D-dimer in serous ovarian cancer was also significantly higher than that of patients with not serous ovarian cancer. The diagnostic accuracy of combined use of serum CA125 and plasma D-dimer in malignant ovarian tumor is higher, especially in serous ovarian tumors. Conclusion: D-dimer combined with CA125 can be used as a more effective marker of malignant ovarian tumors, especially advanced ovarian cancer.