To investigate the expression levels of stromal cell-derived factor-1 (SDF-1) and chemokine receptor 4 (CXCR4) in moderate and severe intrauterine adhesions (IUA) tissues of patients. Methods: From April 2019 to April 2022, 132 patients with moderate and severe IUA diagnosed in hospital who wanted hysteroscopic surgery were selected in study group, including 51 patients with moderate in group A and 81 patients with severe patients in group B. Another 132 patients with uterine mediastinum diagnosed by hysteroscopy were selected in control group during the same period. The general data and sex hormones indexes of all the patients were collected. The expression levels of SDF-1 and CXCR4 proteins of all the patients were detected by immunohistochemistry. Kaplan-Meier was used to analyze the correlation between the expressions of SDF-1 and CXCR4 levels of the patients with IUA and their prognosis after operation. Multivariate Cox regression was used to analyze the influence factors of the prognosis of IUA. Results: The numbers of the pregnancy, delivery, and pregnancy-related uterine operation of the patients in the study group were significantly more than those of the patients in the control group. The positive rates of SDF-1 (81.1%) and CXCR4 (77.3%) of the patients in the study group were significantly higher than those (25.0% and 20.5%) of the patients in the control group. The positive rates of SDF-1 (90.1%) and CXCR4 (87.7%) of the patients in group B were significantly higher than those (66.7% and 60.8%) of the patients in group A (all P＜0.05). In the patients with fail treatment, the proportions of the positive expression of SDF-1 (29.0%) and CXCR4 (31.4%) of the patients were significantly higher than those (12.0% and 6.7%) of the negative expression of SDF-1 and CXCR4 of the patients (all P＜0.001). Cox regression analysis showed that the SDF-1 and CXCR4 levels of the patients with IUA were the independent risk factors of their prognosis of IUA (P＜0.05). Conclusion: The positive rates of SDF-1 and CXCR4 in the IUA tissues of the patients increase. The SDF-1 and CXCR4 levels of the patients are related to the severity and the prognosis of their IUA.