Objective: To investigate the diagnostic value of combined detection of serum neuron-specific enolase (NSE), malignant tumor-specific growth factor (TSGF), ferritin (FERR) and carbohydrate antigen 125 (CA125) in ovarian cancer. Methods: From March 2018 to March 2020, 50 patients with ovarian cancer admitted to our hospital were selected as the ovarian cancer group, 43 patients with benign ovarian lesion as the benign lesions group, and 37 healthy female patients in the same period were selected as the control group. Detect three groups of serum TSGF, CA125, NSE, FERR levels to evaluate the sensitivity and specificity of each serum tumor marker; use ROC curve to analyze TSGF, CA125, NSE, FERR and the combined detection of four tumor markers for the diagnosis value of ovarian cancer. Results: The serum tumor markers TSGF, CA125, NSE and FERR levels in the ovarian cancer group were higher than those in the control group and the benign lesion group, and the differences were statistically significant (P<0.05); the positive rate of single detection of TSGF, CA125, NSE and FERR in the ovarian cancer group was higher than that in the benign lesion group and the control group, the difference was statistically significant (P<0.05); the positive rate of combined detection of 4 serum tumor markers was 82.0%, which was higher than that of any single tumor and the difference was statistically significant (P<0.05); the area under the curve for the diagnosis of ovarian cancer by the combined detection of four tumor markers was 0.913, with the sensitivity of 82% and the specificity of 81.40%, and the sensitivity and the area under the curve were higher than those of the four serum tumor indicators separately detected. Conclusion: The combined detection of CA125, CEA, NSE and TSGF can significantly improve the sensitivity and accuracy of ovarian cancer diagnosis, and its diagnostic value is higher than that of single tumor marker detection.