Objective：To evaluate the predictive value of the neutrophil - to - lymphocyte ratio（NLR）and the systemic immune - inflammation index（SII）in predicting patients with anti - melanoma differentiation - associated gene 5 - positive（anti - MDA5 ⁺ ） dermatomyositis（DM）develop into the rapidly progressive interstitial lung disease（RPILD）. Methods：We retrospectively analyzed the clinical and laboratory data of 124 anti - MDA5 ⁺ DM patients from the First Affiliated Hospital of Nanjing Medical University between March 2019 and September 2023. We identified independent risk factors associated with the development and mortality of RPILD with the Cox regression analysis，and determined the optimal cut-off values for predicting adverse outcomes with the receiver operating characteristic（ROC）curve analysis. Results：Among the 124 patients，36 patients（29.03%）developed RPILD，and 39 patients（31.45%）died during the follow-up period. The results of multivariate Cox regression analysis showed that the elevated NLR was an independent risk factor for RPILD development，while the elevated SII expression was independently associated with the increased mortality of RPILD. Based on the ROC curve analysis，NLR＞6.12 was a predictor for RPILD，and SII ＞875.79 was associated with increased mortality risk of RPILD. Conclusion：Both NLR and SII are accessible，cost-effective，and reliable prognostic indicators for the prognosis of patients with anti-MDA5⁺ DM，providing a valuable guidance for clinical management and risk stratification of the disease.