Background: Endometriosis is a chronic disease associated with disorder of the oxidative balance and chronic inflammation. Although endometriosis is a benign disease, it has the characteristics properties similar to malignant cancer.Methods: The present study aim to investigate the role of glutathione S-transferase Mu class 4 (GSTM4), and tested if 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol (NBDHEX) could regulate GSTM4 expression to affect cell proliferation, migration, invasion and apoptosis in endometriosis. Expression of GSTM4 was detected by immunohistochemistry in 15 cases of endometriosis patients and compared with 15 healthy controls. Primary endometrial cells were analyzed by western blotting (WB) to determine expression of GSTM4, PCNA, MMP-9, Survivin, Bcl-xl, Bax, Keap1 and Nrf2. CCK8 and transwell assays were used to study the effects of GSTM4 and NBEHEX on endometrial cells. The effect on apoptosis was analysised by flow cytometry. Results: The expression of GSTM4 was significantly increased in endometriosis than those from controls (p<0.01). The results suggested that NBDHEX negatively regulates GSTM4 expression, induces cell proliferation, migration, invasion, and promotes cell apoptosis. NBDHEX decreased the expression of GSTM4 (p<0.05), PCNA (p<0.05), MMP-9 (p<0.01), Survivin (p<0.05) and Bcl-xl (p<0.05) , along with increased expression of Bax (p<0.05). The results also showed that NBDHEX decreased the expression of Nrf2 (p<0.05), but had no effect on the expression of Keap1(p>0.05). After transfection with si-GSTM4, the protein level was down-regulated by nearly 70% (p<0.05). Silencing of GSTM4 depressed the proliferation, migration, invasion and gene expression of endometrial stromal cells in patients with endometriosis and controls. Knockdown of GSTM4 interacting with Nrf2 induced apoptosis by decreasing the expression of Survivin (p<0.05), Bcl-xl (p<0.05) and increasing the expression of Bax (p<0.05) , but it did not affect the expression of Keap1(p>0.05) in endometriosis and controls. Conclusions: Inhibition of GSTM4 by NBDHEX suppresses the cell viability growth, migration, invasion and interact with Nrf2 to induce apoptosis, but has no effect on the expression of Keap1 in endometriosis. The use of siRNA to knockdown GSTM4 more accurately confirmed its ability to ameliorate the progression of endometriosis. NBDHEX may have therapeutic potential in the treatment of endometriosis.