To detect the expressions of epidermal growth factor receptor (EGFR) and G protein coupled estrogen receptor (GPER) in endometrial tissue of the women with endometriosis (EMT), and to explore the relationship between EGFR level and GPER level and their clinical significance. Methods: From Jan 2018 to Jan 2020, 42 patients with EMT were selected in observation group, and 31 patients with hysterectomy because of leiomyoma of uterus were selected in control group. The expression of protein of EGFR and GPER in endometrial tissue was detected by immunohistochemistry, and the expression levels of EGFR and GPER mRNA in the tissue of EMT and normal endometrium were detected by qRT PCR. The correlation between EGFR mRNA expression and GPER mRNA expression in endometrial tissue of the women with EMT was analyzed. Results: The expression levels of EGFR and GPER mRNA and protein in ectopic and eutopic endometrium of EMT were significant higher than those in normal endometrium (P＜0.05), while there were no significant difference in the expression levels of EGFR, GPER mRNA and protein between ectopic and eutopic endometrium of EMT (P＞0.05). In eutopic endometrium of EMT, the protein positive expression rates of EGFR and GPER in proliferative phase endometrium was significant higher than that in secretory phase endometrium (P＜0.05). In ectopic endometrium of the women with EMT, the positive expression rate of EGFR and GPER in endometrium of the women with stage III-IV of EMT was significant higher than that of the women with stage I-II of EMT (P＜0.05). Pearson analysis showed that the expression level of EGFR mRNA were positively correlated with the expression level of GPER mRNA (r=0.531, P=0.000). Conclusion: The expresses of EGFR and GPER in endometrial tissue of the women with EMT are higher, which may play a synergistic role in the occurrence and clinical stage of EMT.