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Hypoxia plays a vital role in the progression of endometriosis. Additionally, integrin-mediated aberrant adhesion is also essential for establishment of endometriotic lesions. In this study, we sought to determine the function of hypoxia in integrin-mediated adhesion of endometrial stromal cells (ESCs) in endometriosis. The expressions of adhesion molecule integrins (integrin a5, integrin aV, integrin ß3, and integrin ß5) were determined in 15 normal endometria and 15 paired eutopic and ectopic endometria by immunohistochemistry. Thirteen primary ESCs from patients with peritoneal endometriosis in the proliferative phase were cultured under a hypoxic (1% O2) or normoxic (21% O2) environment, and the expression levels of hypoxia-inducible factor (HIF)-1a, transforming growth factor (TGF)-ß1, and integrins were detected by quantitative reverse transcription polymerase chain reaction and western blot. The alteration of integrins in endometriotic mouse models were also explored. Our results demonstrated that HIF-1aand integrins were highly expressed in ESCs of endometriotic lesions compared with ESCs of eutopic and normal endometrium. Hypoxia treatment significantly increased ESC adhesion abilities and integrin expression, which were positively correlated with TGF-ß1 expression. Both TGF-ß1 and hypoxia enhanced ESC adhesion properties, whereas hypoxia combined with TGF-ß1 receptor inhibitor inhibited ESC adhesion. Knockdown of HIF-1aattenuated TGF-ß1/Smad signaling activation and integrin expression and reduced ESC adhesion. Higher expression levels of HIF-1a, TGF-ß1, and integrins were detected in endometriotic cysts from mice models. Our findings provide a novel insight of endometriosis that the hypoxic microenvironment stimulates ESCs to produce excessive TGF-ß1 and activates the TGF-ß1/Smad signaling pathway, thus enhancing integrin expression and the adhesion ability of ESCs.Hypoxia enhances integrin expression and the adhesion ability of ESCs via stimulating ESCs to produce excessive TGF-ß1 and activating the TGF-ß1/Smad signaling pathway in endometriosis.