The potential important of epithelial-mesenchymal transition in the pathogenesis of COPD is currently intensely debated. EMT-associated splicing is likely regulated by several splicing factors including epithelial-specific RNA binding protein. Our previous studies suggest NOX4 as a mechanism interacting with TGF?1 in the pathogenesis of COPD. We want to investigate the roles of NOX4 and ESRP1 in COPD and their crosslink. A total of 23 COPD patients and 19 individuals with normal lung function were recruited. The expression of FN, LN, ?-SMA, COI-I were higher in COPD groups, with The expression of ESRP1 and NOX4 being higher in COPD groups. Serum SOD3 levels were lower in COPD groups and MDA levels were higher in control groups. The same results got in cigarette smoke-induced mouse models and in vitro cell models. Further, After pretreatment of BEAS2B cells with NAC, the levels of EMT-related proteins of ESRP1 and NOX4 in the NAC+TGF?1 group were lower in TGF?1 group. And siRNA knockdown ESRP1, siRNA-ESRP1+TGF?1 group showed lower protein expression levels of NOX4,N-Ca,?-SMA than TGF?1 group. Together, adenovirus knockdown NOX4 expression, shNOX4+TGF?1 group ESRP1, FN, N-Ca and ?-SMA protein expression levels were lower than TGF?1 group. These data suggest that the process of EMT is active in COPD patients, and NOX4 and ESRP1 were involved in the process of EMT in COPD.