Objective: To study the expression level of anti-melanoma differentiation gene 5 antibody (anti-MDA5 antibody) in serum of idiopathic inflammatory myopathy (IIM) patients associated with interstitial lung disease (ILD), and to explore the relationship between anti-MDA5 antibody and clinical characteristics, severity and 6-month mortality of IIM-ILD patients for providing laboratory evidences to delineate new immune intervention pathway. Methods: The expression of anti-MDA5 antibody in serum of 104 patients with IIM or IIM-ILD, including polymyositis 4 cases, dermatomyositis 8 cases, amyopathic dermatomyositis, 7 cases, polymyositis-ILD 17 cases, dermatomyositis-ILD 25 cases, amyopathic dermatomyositis-ILD 43cases, and normal control group was detected by ELISA, and the relationships between anti-MDA5 antibody and lung function [FVC% and DLCO/SB (single breath, carbon monoxide diffusing capacity)], lung structure [HRCT score (high resolution CT score)] and 6-month survival were analyzed. Results: In patients with amyopathic dermatomyositis (ADM), the serum level of anti-MDA5 antibody was higher than that of normal controls, patients with dermatomyositis (DM), IIM not associated with ILD and polymyositis (PM) with ILD(P<0.005). Compared with DM-ILD patients, the serum level of anti-MDA5 antibody in patients with ADM-ILD was increased (P<0.05). There was no correlation between anti-MDA5 antibody level and lung function in patients with IIM (FVC% r=-0.04425 P=0.7579, DLCO/SB, r=-0.06839 P=0.6335), and was positively correlated with lung structural changes (r=0.3879 P=0.0002). The 6-month mortality of IIM patients with positive anti-MDA5 antibody was significantly different from that of anti-MDA5 antibody negative patients (P=0.0002). Conclusions: The anti-MDA5 antibody level detected by ELISA is closely correlated with lung function, severity of lung structural damage and mortality in patients with DM-ILD, especially ADM-ILD.