Objective: To study the possible diagnostic value of soluble CD146 (sCD146) in patients with ovarian cancer. Methods: A total of 33 patients with benign ovarian tumor and 30 with ovarian cancer from Department of Obstetrics and Gynecology, Anzhen Hospital were respectively selected as observation group A and observation group B, while 31 healthy women from Medical Center, Anzhen Hospital were served as control group. There was no significant difference in the age among three groups. Enzyme immunoassay and chemiluminescence were used to detect the expression of sCD146 and CA125, respectively. Results: The sCD146 level was lower in observation group A and observation group B when compared with control group (P<0.01). Moreover, serum sCD146 in observation group B was further lower than that in observation group A (P<0.05). The CA125 level increased in observation group B compared with those in control group and observation group A (P<0.001). And the CA125 level in observation group A was markedly higher than that in control group, and the difference was statistically significant (P<0.001). If either single target was tested to be positive, it was advisable to choose combined detection of CA125 and sCD146, which could improve the diagnostic specificity. Conclusion: sCD146 may provide a potential marker for the diagnosis and treatment of patients with ovarian cancer.