[Abstract] Objective: To investigate the relationship between dynamic changes of serum CA125 or HE4 and patients' progression-free survival (PFS) before and after surgery and during chemotherapy. Methods: A retrospective analysis of clinical data of ovarian cancer patients treated with standardized treatment in the gynecologic oncology ward of the First People's Hospital of Shanghai was performed. The collected information included serum CA125 and HE4 levels before and after chemotherapy and during at least two cycles of chemotherapy, platinum sensitivity, and PFS. Statistical methods used included chi-square test, t-test, logistic regression analysis, and Cox proportional hazards regression analysis. Results: 1) Analysis of 117 patients with high-grade serous ovarian cancer suggests that CA125 and HE4 positivity are associated with higher stage, greater ascites volume, less satisfactory cytoreduction, and positive ascites cytology, while the mean values of CA125 and HE4 showed no significant difference in different platinum sensitivity states and PFS groups (P>0.05). 2) Cox regression analysis verified that both CA125 and HE4 are prognostic risk factors (HR values were 4.29 and 1.77, P=0.01 and 0.049, respectively). 3) Patients with both CA125 and HE4 positive and those with only CA125 positive showed no significant difference in prognosis (P>0.05). 4) The half-life of CA125 and HE4 was calculated using the formula t1/2=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 poml/L, 12 U/L, 35.2 pmol/L, 21 days, and 25 days, respectively. The prognostic analysis showed that except for the lowest value of HE4, which was not related to prognosis, all others were related to prognosis. The HR value for CA125 half-life >21 days was the highest at 3.28, with a median PFS decrease of 57.5%, P<0.001. 5) 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.Conclusions: CA125 half-life, CA125 lowest value, and failure of CA125 to return to normal after the third cycle of chemotherapy have certain clinical value for predicting recurrence within three years. However, the value of these indicators in predicting platinum sensitivity remains to be explored further.