Objective: To explore the relationship between anticoagulant factor Xa activity, serum endothelin-1 (ET-1), solute carrier family 39 member 11 (SLC39A11) and the occurrence of deep vein thrombosis (DVT) in the lower extremities of patients with gynecological malignancies. Methods: A total of 270 patients with gynecological malignant tumors (malignant group) and 230 patients with gynecological benign tumors (benign group) were selected as the research subjects. The anti-Xa factor activity and the levels of serum ET-1 and SLC39A11 were determined and compared. Lasso-Logistic regression was used to analyze the influencing factors of lower extremity deep vein thrombosis (DVT). In addition, the predictive value and clinical significance of anti-Xa factor activity, serum ET-1, and SLC39A11 levels in the occurrence of lower extremity DVT in patients with gynecological malignant tumors were analyzed. Results: Compared with the benign group, the malignant group had lower anti-factor Xa activity and higher levels of serum ET-1 and SLC39A11 (P < 0.05). Lasso-Logistic regression analysis showed that D-dimer, antithrombin Xa activity, serum ET-1, and SLC39A11 were the influencing factors for the occurrence of lower extremity DVT in patients (P < 0.05). The area under the curve (AUC) of anti-Xa factor activity, serum ET-1, SLC39A11 and their combination in predicting lower extremity deep vein thrombosis (DVT) in patients with gynecological malignancies were 0.844, 0.799, 0.771 and 0.931, respectively, all of which had good predictive value within the risk threshold range of 0.06 to 0.83. The combined prediction of anti-factor Xa activity, ET-1, and SLC39A11 for lower extremity DVT in patients with gynecological malignancies had a significantly greater net benefit than that of a single indicator. Conclusion: The anti-Xa factor activity, ET-1, and SLC39A11 are related to the occurrence of DVT in patients with gynecological malignant tumors. The combined detection of the three has a good application prospect in the prediction of postoperative DVT.