Objective: To explore the application value of combined detection of serum squamous cell carcinoma antigen (SCC Ag), human epididymal protein 4 (HE4), and soluble programmed death ligand 1 (sPD-L1) in monitoring postoperative recurrence of cervical cancer. Methods: 80 cervical cancer patients admitted from March 2022 to May 2023 were selected, all of whom underwent surgical treatment. They were followed up for 2 years in the outpatient department, and 21 patients who relapsed during the 2-year postoperative period were selected as the recurrence group, while the remaining 59 patients were selected as the non recurrence group. The clinical data of the two groups were compared. The expression levels of SCC Ag, HE4 and soluble PD-L1 in serum were detected by electrochemiluminescence immunoassay, enzyme-linked immunosorbent assay and flow cytometry. Use logistic regression to analyze the factors affecting postoperative recurrence of cervical cancer, and establish receiver operating characteristic (ROC) curves to analyze the predictive value of combined detection of serum SCC Ag, HE4, and soluble PD-L1 in postoperative recurrence of cervical cancer. Results: There were no significant differences in age, pathological type, and surgical approach between the recurrent and non recurrent groups (P>0.05). The International Federation of Obstetrics and gynecology (FIGO) staging, tumor size and depth of invasion were significantly different between the recurrence group and the non recurrence group (P<0.05); The serum levels of SCC Ag, HE4, and sPD-L1 in the recurrent group were higher than those in the non recurrent group (P<0.05); FIGO staging, tumor size, depth of invasion, SCC Ag, HE4, and sPD-L1 elevation are all independent influencing factors for cervical cancer recurrence (P<0.05); The cutoff values for predicting postoperative recurrence of cervical cancer using SCC Ag, HE4, and sPD-L1 are 2.15 ng·mL-1, 75.00 pmol·L-1, and 28.73 pg·mL-1, respectively. The combined sensitivity and specificity of the three methods for predicting postoperative recurrence of cervical cancer are 64.69% and 85.76%, respectively. Conclusion: The combined detection of serum SCC Ag, HE4, and soluble PD-L1 can predict early postoperative recurrence of cervical cancer and provide reference for the development of clinical treatment plans.