Objective To investigate the expression and correlation of COX-2 and α -Synuclein in endometrial tissues of patients with endometriosis and infertility. Methods From June 2016 to August 2017, 54 patients with endometriosis and infertility who were treated in our hospital were included in the observation group, 28 patients and 26 patients in the proliferative and secretory phases. 54 patients without endometriosis who underwent hysterectomy at the same time as cervical lesions in our hospital were included in the control group, including 27 patients in the proliferative and 27 patients in secretory phases. The in-situ, ectopic, and normal endometrial tissues of the above subjects were stripped and collected. The expression and distribution of COX-2 and α -Synuclein in the samples were detected by immunohistochemistry. The RNA and protein expressions of COX-2 and α -Synuclein were detected by RT-RCR and Western blotting. The Spearman method was used to analyze correlation between COX-2 and α-Synuclein expression. Results Cox-2 and α-Synuclein in the observation group increased significantly in the proliferative and secretory membrane tissues compared with the control group, with statistically significant differences (P < 0.05). The expressions of COX-2 and α-Synuclein in the endometrial tissues of the two groups were significantly higher in the secretory stage than in the proliferative stage (P < 0.05). In addition, the expression of COX-2 in the ectopic endometrial tissues of the observation group was positively correlated with the expression of l-synuclein (rs = 0.885, P < 0.05). Conclusions COX-2 and α -Synuclein are abnormally overexpressed in the endometrial tissue of patients with endometriosis, have positive correlation with each other, suggesting that the synergistic overexpression of the two may promote the development of endometriosis and lead to infertility, in which they play an important role, and is expected to become an important target for the diagnosis and gene therapy of this disease.