To investigate between the expressions of E-cadherin and vascular endothelial growth factor (VEGF) in the endometrial lesions of patients and their survival situation. Methods: The clinical data of 607 patients with endometrial lesions admitted to the hospital from January 2018 to January 2023 were selected in this study. Based on the postoperative pathological results, these patients were divided into group A (patients with benign endometrial lesion) and group B (patients with malignant endometrial lesion). According to the follow-up results, the patients in group B were divided into group B1 (patients with survival) and group B2 (patients with death). The expressions of E-cadherin and VEGF in the endometrial lesions of the patients in these groups were detected by immunohistochemistry, and the correlation between which of the patients in group B and their survival prognosis was analyzed. Results: The positive rate of Ecadherin (30.0%) of the patients in group B was significantly lower than that (78.8%) of the patients in group A, and the positive rate of VEGF (68.0%) of the patients in group B was significantly higher than that (29.8%) of the patients in group A (all P<0.05). During the follow-up of 10-59 months (median of 29 months) after surgery, 36 (24.0%) patients in group B of 150 patients had died. The overall survival time of the patients with positive E-cadherin was significantly longer than that of the patients with negative E-cadherin (Log rank χ2=8.033). The overall survival time of the patients with positive VEGF were significantly shorter than that of the patients with negative VEGF (Log rank χ2=8.343). The proportions of FIGO stage Ⅲ-Ⅳ, the tumor low differentiation, the tumor invasion depth ≥1/2, the tumor invasion of the lower uterine segment, the lymph node metastasis, the negative expression of E-cadherin and the positive expression of VEGF of the patients in group B2 were significantly higher than those of the patients in group B1. The negative expression of E-cadherin and the positive expression of VEGF of the patients with endometrial malignant lesions were the independent risk factors of their prognosis (P<0.05). The area under the curve and the sensitivity of the E-cadherin negative expression combined with the VEGF positive expression of the patients for differentiating their benign and malignant endometrial lesions were 0.848 and 86.4%. Conclusion: The negative expression of E-cadherin and the positive expression of VEGF of the patients are closely related to the occurrence and development of their malignant endometrial lesions. The E-cadherin negative expression combined with the VEGF positive expression of the patients with malignant endometrial lesions for evaluating their prognosis has certain value.