Amyotrophic lateral sclerosis (ALS) is among the severe neuro degenerative diseases that lack widely available effective treatments. As the disease progresses, patients lose the control of voluntary muscles. Although the neuronal degeneration is the cause of this disease, the failure mechanism is still unknown. In order to seek genetic mechanisms that initiate and progress ALS, the association of microRNA (miRNA) expression with this disease was considered. Serum miRNAs from healthy controls, sporadic ALS (sALS), familial ALS (fALS) and ALS mutation carriers were investigated. Principal component analysis (PCA)-based unsupervised feature extraction (FE) was applied to these serum miRNA profiles. As a result, we predict miRNAs that can discriminate patients from healthy controls with high accuracy. Thus, these miRNAs can be potential prognosis miRNA biomarkers for ALS.