Objective: To investigate high mobility group box1 (high mobility group box1) in endometrial tissue of patients with intrauterine adhesion (IUA) Relationship between the expression of HMGB1, high mobility group protein A2 (HMGA2) and epidermal growth factor receptor (EGFR) and the disease and prognosis. Methods: 68 IUA patients admitted to our hospital from August 2021 to August 2023 who underwent intrauterine adhesion separation were selected as the IUA group. In addition, 60 patients with normal uterine morphology and no adhesion after hysteroscopy were selected as the control group. The expressions of HMGB1, HMGA2 and EGFR in the two groups were detected by immunohistochemistry. The relationship between the expression of HMGB1, HMGA2 and EGFR and the disease of IUA patients was analyzed. Multivariate logistic regression was used to analyze the adverse prognostic factors of IUA. Results: The positive expression rate of HMGB1 in endometrial tissues of IUA group was significantly lower than that of control group, and the positive expression rates of HMGA2 and EGFR were significantly higher than those of control group (P<0.05). 68 IUA patients were divided into mild group (19 cases), moderate group (28 cases) and severe group (21 cases) according to the severity of intrauterine adhesions. With the aggravation of the disease, the positive expression rates of HMGB1 in endometrial tissues of IUA patients decreased successively, and the positive expression rates of HMGA2 and EGFR increased successively, with significant differences among groups (P<0.05). After 1 year of follow-up, 17 cases (25.00%) of IUA recurred and were included in the relapse group. Fifty-one cases (75.00%) without recurrence were included in the recurrence group. Univariate analysis showed that poor prognosis was related to abortion history, preoperative menstrual volume, adhesion range, adhesion nature, HMGB1, HMGA2 and EGFR expression (P<0.05), but not related to age and course of disease (P>0.05). Multivariate Logistic regression analysis showed that history of abortion >3 times, preoperative amenorrhea, adhesion range >2/3, adhesion nature muscle, negative expression of HMGB1, positive expression of HMGA2 and EGFR were risk factors for postoperative recurrence (P<0.05). Conclusion: The negative expression of HMGB1 and positive expression of HMGA2 and EGFR in endometrial tissues of IUA patients are related to the degree of disease and postoperative recurrence of patients, and the detection of the three expressions is helpful to evaluate the degree of disease and poor prognosis of patients.