Background: Venous thromboembolism (VTE) is an important complication in patients with malignant tumors.Its exact diagnosis and treatment are still lacking.We used a high-sensitive chemiluminescence method to detect thrombin–antithrombin III complex (TAT),plasmin-α2-plasmininhibitor complex (PIC), thrombomodulin (TM),and tissue plasminogen activator–inhibitor complex(t-PAIC) in combination with D-dimer and fibrin degradation product (FDP) to analyze their diagnostic and prognostic value in patients with malignant tumors. Methods: In total, 870 patients with confirmed malignant tumors were included, 82 of whom had suspected VTE;200 healthy individuals were classified as the control group. The TAT, PIC,TM, and t-PAIC were detected using Sysmex HISCL5000 automated analyzers, whereas FDP and D-dimer were detected using Sysmex CS5100 coagulation analyzer.Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficiency.Survival probabilities were determined using Kaplan–Meier analysis, and multivariate analyses were performed using a Cox regression model. Results: Compared with healthy controls,patients with malignant tumors showed significantly elevated TAT,PIC,TM,t-PAIC,D-dimer, and FDP. Similarly, compared with patients in the non-thrombosis group, those in the thrombosis group showed significantly elevated levels of the above mentioned markers. Logistic regression analysis showed that TAT, PIC, TM, t-PAIC, D-Dimer, and FDP were all associated with VTE.ROC analysis showed that “TAT+PIC+TM+t-PAIC+D-dimer+FDP”showed the highest sensitivity and specificity.Patients with elevated TAT,PIC,TM, and t-PAIC had a significantly shorter survival.Multivariate Cox survival analysis showed that TM and t-PAIC were significantly associated with poor prognosis.In addition, the incidence of VTE was significantly lower in patients with malignant tumors who were treated with low-molecular-weight heparin (LMWH), and their survival period was significantly longer than that of patients with malignant tumors who were not treated with LMWH. Conclusion: TAT, PIC, TM, and t-PAIC combined with D-dimer and FDP were better than the application of a single marker in the diagnosis of VTE in patients with malignant tumors.TAT and PIC can be used as sensitive markers in the diagnosis of VTE but not as prognostic markers. TM and t-PAIC might be independent prognostic indicators in patients with malignant tumors, regardless of the state of thrombus.