Abstract: Objective: To analyze the expression of serum immunoglobulin G4(IgG4) and 25-hydroxyvitamin D25(OH)D in endometrial cancer and its correlation with pathological features. Methods: From April 2021 to June 2023, 90 patients with endometrial cancer in Shijiazhuang People's Hospital in Hebei province were selected as endometrial cancer group, 50 patients with benign endometrial lesions in the same hospital during the same period were selected as benign lesion group, and 50 healthy people in the same hospital during the same period were selected as healthy group. The serum IgG4, 25(OH)D levels of the three groups were compared, the correlation between the two indexes was analyzed by Pearson correlation, and the receiver operating characteristic(ROC) curve was drawn to analyze the value of serum IgG4, 25(OH)D and their combination in diagnosing endometrial cancer. The serum IgG4 and 25(OH)D levels of patients with different pathological features(age, FIGO stage, degree of differentiation, depth of myometrial infiltration, lymph node metastasis and iron deficiency anemia) were compared, and the correlation between the two indexes and pathological features was analyzed by point-and-column correlation. Results: The serum IgG4 and 25(OH)D levels in the endometrial cancer group were lower than those in the benign lesion group and the healthy group(P<0.05). The ROC curve showed that serum IgG4, 25(OH)D and the area under the ROC curve(AUC) of combined diagnosis of endometrial cancer were 0.839(95% CI:0.0.783-0.895), 0.801(95% CI:0.739-0.864) and 0.851(95% CI:0.798-0.905), respectively. Pearson correlation showed that serum IgG4 was positively correlated with 25(OH)D levels(r=0.440, P<0.001). The serum IgG4 and 25(OH)D levels in the FIGO stage Ⅲ-Ⅳ, low differentiation, myometrial infiltration depth ≥ 1/2, lymph node metastasis and iron deficiency anemia were lower than those in the FIGO stage Ⅰ-Ⅱ, moderate and high differentiation, myometrial infiltration depth<1/2, no lymph node metastasis and no deficiency iron anemia(P<0.05). Point-column correlation showed that serum IgG4 and 25(OH)D levels were negatively correlated with the FIGO stage, depth of myometrial infiltration, lymph node metastasis and iron deficiency anemia in patients with endometrial cancer(P<0.05), and positively correlated with differentiation degree(P<0.05). Conclusion: The levels of serum IgG4 and25(OH)D in patients with endometrial cancer are low. They are closely related to the pathological features such as FIGO stage, degree of differentiation, depth of myometrial infiltration, lymph node metastasis and iron deficiency anemia, and can be combined to effectively diagnose endometrial cancer.