Abstract: Objective To explore the role of calcium binding protein S100A7 in the pathogenesis of ovarian endometriosis (OEM).Methods A total of 42 OEM patients and 42 patients with fallopian tube obstruction were selected and 5 ml of fasting venous blood were collected. Among them, 23 OEM patients and 23 patients with fallopian tube obstruction were selected for the collection of endometrial tissues. Then, in situ endometrial stromal cells (ESC) from the endometrial tissues were primarily cultivated in vitro. Lentivirus transfection technology was used to interfere with the expression of S100A7 or overexpress S100A7 in ESC. The levels of S100A7 and NF-κB in the endometrial tissues, as well as the expression of S100A7 in ESC were detected by qRT-PCR. The amounts of molecules in the NF-κB signaling pathway, such as matrix metalloproteinase 9 (MMP9), G1/S- specific cyclin -D1 (Cyclin D1), activated cysteine-aspartate protease 3 (Cleaved-caspase3), nuclear-nuclear transcription factor-κBp65 (N-NF-κBp65), and cytoplasmic-nuclear transcription factor-κBp65 (C-NF-κBp65) were detected by Western blot. The levels of serum S100A7 and the contents of TNF-α and IL-6 in the cell supernatant were examined by ELISA. Then, CCK-8 assay, flow cytometry, Annexin V-FITC/PI double staining, and Transwell assay were used to detect changes in biological behaviors such as cell proliferation, cycle, apoptosis, and invasion before and after transfection.Results Compared with patients with fallopian tube obstruction, OEM patients showed significantly up-regulated levels of S100A7 and NF-κB in the endometrial tissues (P<0.001) which were positively related. In the ESC of OEM patients, the expression of S100A7 and N-NF-κBp65 remarkably increased (P<0.001), while the expression of C-NF-κBp65 decreased (P<0.001). Interfering with S100A7 expression resulted in reduced expression of S100A7 mRNA in ESC (P<0.001), with decreases in the ability of cell proliferation and invasion, increased apoptotic ability, reduced expression of S100A7, N-NF-κBp65, MMP9 and Cyclin D1, increased expression of C-NF-κBp65 and Cleaved-caspase3, and decreased levels of TNF-α and IL-6 in cell supernatant. In contrast, overexpression of S100A7 in ESC resulted in significantly up-regulated S100A7mRNA (P<0.001), with biological characteristics and protein expression that were different from S100A7 interference and reversed after addition of an NF-κB inhibitor.Conclusions S100A7 is involved in the pathogenesis of OME through activating the NF-κB signaling pathway in endometrial stromal cells, and regulating the proliferation activity, invasiveness, and apoptosis rate of ESC.