To explore the effect of hysteroscopic and laparoscopic surgery combined with high-potency progesterone for treating patients with endometrial cancer. Methods: 110 patients with endometrial cancer were randomly selected from hospital and were divided two groups (55 cases in each group)according to the numerical table method between June 2017 and June 2022. The patients in the two groups were given treatment of high-efficiency progesterone, and the patients in the observation group were given hysteroscopic and laparoscopic surgery additionally. The levels of serum carbohydrate antigen 199 (CA199)and inflammatory factors of the patients in the two groups were detected. The efficacy, the adverse reactions, and the recurrence rate of endometrial cancer of the patients were compared between the two groups. Results: The total effective rate (81.8%)of the patients in the observation group was significantly higher than that (45.5%)of the patients in the control group. After treatment, the CA199 level of the patients in both groups had decreased significantly, and which (10.37±1.93 U/ml)of the patients in the observation group was significantly lower than that (23.28±2.73 U/ml)of the patients in the control group. The expressions of inflammatory factors of the patients in both groups had decreased significantly, and which of the patients in the observation group was significantly lower than that of the patients in the control group (all P＜0.05). There was no significant difference in the incidence of adverse reactions (14.6% vs. 21.5%)of the patients between the two groups (P＞0.05). The recurrence rate of endometrial cancer (5.5%)of the patients in the observation group was significantly lower than that (27.3%)of the patients in the control group (P＜0.05). Conclusion: Hysteroscopic and laparoscopic surgery combined with high-efficiency progesterone for treating the patients with endometrial cancer can increase the therapeutic effect, which can effectively improve the expressions of tumor serum factors and inflammatory factors, reduce the recurrence rate of endometrial cancer, with good safety.