Objective:To investigate the expression and correlation of hepatocyte growth factor (HGF), fibroblast growth factor 2 (FGF-2), and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway in patients with endometriosis. Methods Eighty cases of ovarian chocolate cyst wall tissue samples obtained through laparoscopic surgery at the First Affiliated Hospital of Bengbu Medical University from April 2023 to April 2024 were collected as the ectopic group, and 65 normal endometrial tissue samples from the same period were selected as the control group. The expression of HGF, FGF-2, and PI3K/AKT in both groups was analyzed by immunohistochemistry, and the correlation between the three and the clinical and pathological characteristics of EMs patients was analyzed. The metric data of normal distribution is represented by xˉ± s, and the comparison of means between two groups is conducted using independent sample t-test. The correlation between the two variables was analyzed using Spearman correlation analysis. Using a multiple Logistic regression model to analyze the influencing factors of recurrence in patients with endometriosis. P<0.05 indicates a statistically significant difference. Results:(1) There was no significant difference in the general data (age, height, body mass, body mass index, cyst size) between the ectopic group and the control group ( t values were 1.81, 0.99, 0.83, 0.95, and 1.90, respectively; P values were 0.072, 0.322, 0.409, 0.345, and 0.059, respectively). (2) HGF, FGF-2 and PI3K were mainly expressed in cytoplasm, among which the positive rates of HGF, FGF-2 and PI3K in ectopic group were 78.75% (63/80), 61.25% (49/80) and 71.25% (57/80), respectively. The positive rates of the control group were 58.46% (38/65), 38.46% (25/65) and 47.69% (31/65), respectively, and there was significant difference between the two groups ( χ2 values were 6.98, 7.45, and 7.44, respectively; P values were 0.008, 0.006, 0.006, respectively ). (3) The expressions of HGF, FGF-2 and PI3K were correlated with the clinical stage of EMs patients ( χ2 values were 6.17, 4.30, and 8.65 , respectively; P values were 0.013, 0.038, and 0.003, respectively). However, there was no correlation with age, BMI, cyst size, reproductive history, menstrual cycle, dysmenorrhea degree or place of residence (all P>0.05); (4) The expression of HGF and FGF-2 in ectopic patients was positively correlated ( r=0.590, P<0.05), HGF was positively correlated with PI3K expression ( r=0.750, P<0.05), FGF-2 was positively correlated with PI3K expression ( r=0.629, P<0.05). (5) Multivariate Logistic analysis of recurrence factors in EMs patients showed that FGF-2 was a protective factor for recurrence in EMs patients ( OR=0.201,95% CI 0.048-0.837, P=0.027). Conclusion:The expression of HGF, FGF-2, and PI3K/AKT pathways is upregulated in patients with endometriosis, which may be related to the occurrence and development of the disease. They are expected to play an important role in the diagnosis, staging, and treatment of endometriosis in the future.