Objective：To investigate the dynamic changes of serum carbohydrate antigen 125（CA125）and human epididymal protein 4（HE4）levels before and after surgery and during chemotherapy，and their relationship with progression-free survival（PFS） and platinum sensitivity in patients with ovarian cancer. Methods：A retrospective analysis was conducted on serum CA125 and HE4 levels before surgery，before chemotherapy，and at least twice during chemotherapy in standardized treated patients with ovarian cancer in the gynecologic oncology department of the First People’s Hospital Affiliated with Shanghai Jiao Tong University School of Medicine. Data on platinum drug sensitivity and PFS were collected. The main statistical methods included chi-square test，t-test， logistic regression analysis，and Cox proportional hazards regression analysis. Results：The analysis of 117 patients with high -grade serous ovarian cancer suggested that CA125 and HE4 positivity were associated with higher stage，greater ascites volume， unsatisfactory surgical debulking，and positive ascites cytology. Cox regression analysis verified that both CA125 and HE4 are prognostic risk factors（OR=4.29，P=0.010；OR=1.77，P=0.049）. Patients with both CA125 and HE4 positive and those with only CA125 positive showed no significant difference in prognosis（P ＞ 0.05）. The half-life of CA125 and HE4 were calculated using the formula t_1/2=t₁/ [ 2×lg（c₁/c₂）]. The optimal cut-offs for preoperative and postoperative CA125 and HE4，and the half-life of CA125 and HE4 were determined by X-tile and were 436 U/L，400 pmol/L，12 U/L，35 pmol/L，21 days，and 25 days，respectively. The prognostic analysis showed that except for the lowest value of HE4，all other factors were related to prognosis. The highest HR value was 3.28 for CA125 half -life ＞21 days，with a decrease of 57.5% in median PFS（P ＜ 0.001）. The area under the curve（AUC）was calculated by plotting the receiver operating characteristic（ROC）curve. ROC curve analysis showed that CA125 half-life ＞21 days （AUC=0.76），CA125 lowest value ＞12 U/L（AUC=0.70），and failure of CA125 to return to normal after the third cycle of chemotherapy（AUC=0.71）have certain clinical value for predicting recurrence within three years，with sensitivities of 71.8%，68.3%， and 68.2%，and specificities of 79.6%，71.7%，and 72.6%，respectively. Conclusion：CA125 half -life，the lowest value of CA125 during chemotherapy，CA125 not returning to normal after the third cycle of chemotherapy，and having≥2 positive indicators among the 6 indicators have certain clinical value in predicting recurrence within 3 years. Further exploration is needed to assess their value in predicting platinum sensitivity.