Abstract: Objective To explore the correlation between serum human epididymis protein 4(HE4), carbohydrate antigen 125(CA125), human cartilage glycoprotein 39(YKL-40)levels and pathological features in patients with ovarian cancer. Methods The serum samples of 80 patients with epithelial ovarian cancer(epithelial ovarian cancer cell group), 40 patients with benign epithelial ovarian tumor(benign ovarian tumor cell group)and 40 healthy women(control group)were collected. The contents of serum HE4 and YKL-40 were detected by enzyme-linked immunosorbent assay(ELISA), and CA125 content was detected by electrochemiluminescence immunoassay. The sensitivities of serum YKL-40, HE4 and CA125 in the diagnosis of ovarian cancer were analyzed, and the optimal limits of serum HE4, CA125 and YKL-40 were determined. Results For control group, the benign ovarian tumor group and the epithelial ovarian cancer group, there were significant differences in contents of YKL-40, HE4 and CA125 between every two groups(P<0.01). The content of YKL-40- was closely related to pathological type(serous type, mucinous type), lymph node metastasis and pathological grade in patients with epithelial ovarian cancer(P<0.05), and the contents of serum HE4 and CA125 were closely related to pathological type(serous type, mucinous type), clinical stage, pathological grade and lymph node metastasis(P<0.05). The survival rates of ovarian cancer patients with positive results of YKL-40, HE4 and CA125 were significantly lower than those with corresponding negative results(P<0.05). The optimal critical values of HE4, CA125 and YKL-40 were 101.200 pmol/L、95.200 U/mL、53.600 ng/mL respectively, and the Youden indexes were 0.852, 0.547 and 0.749 respectively. The sensitivities of HE4, CA125 and YKL-40 were 91.5%, 87.0% and 72.0% respectively, the sensitivity of the combined diagnosis was 96.5%, and there were significant differences(P<0.05). The specificities of HE4, CA125 and YKL-40 were 92.0%, 93.0% and 95.0% respectively, the specificity of the combined diagnosis was 85.0%, and there were significant differences(P<0.05). Conclusion The levels of serum HE4, CA125 and YKL-40 in patients with ovarian cancer are closely related to the occurrence and poor prognosis of ovarian cancer.