〔Abstract〕 Objective Exploring the clinical and pathological significance of mismatch repair (MMR) protein expression loss in endometrial cancer (EC). Methods Fifty postoperative paraffin embedded endometrial tissue samples from EC patients at Huizhou First Hospital from March 2019 to December 2022 were selected. Immunohistochemical detection was used to detect the expression of MMR protein, including MLH1, MSH2, MSH6, and PMS2. The expression loss rate of MMR protein was observed, and the expression loss of MMR protein was compared among different ages and EC pathological characteristics. Results (1) The incidence of MMR protein expression loss in 50 EC patients was 36.00 %. The expression deletion rates of MMR protein MLH1, MSH2, PMS2, and MSH6 were 22.00 %, 6.00 %, 30.00 %, and 6.00 %, respectively. Among them, there were 4 cases of single deletion (8.00 %) and 14 cases of two expression deletions (18.00 %). (2) The expression rate of MMR protein deficiency in EC patients ≤ 50 years old (56.00 %) was higher than that in EC patients > 50 years old (16.00 %), and the difference was statistically significant (P < 0.05). (3) There was no statistically significant difference in the expression of MMR protein among patients with different levels of cell differentiation, muscle infiltration, and lymph node metastasis (P > 0.05). Conclusion The expression loss rate of MMR protein in EC is relatively high, with PMS2 expression loss being the main factor. Moreover, the expression loss rate of MMR protein is higher in EC patients ≤ 50 years old. Therefore, it is necessary to pay attention to early screening for related heritability in young women.