Hexaploid bread wheat (Triticum aestivum) is one of the major crops grown and consumed all over the world. Elevated soil salinity causes reduction in crop yield and quality; therefore, several strategies were developed to improve salt-tolerant cultivars. MicroRNAs (miRNAs), small and non-coding RNAs, regulate gene expression at post-transcriptional level and play important roles in stress tolerance. Here, we used a broad-range miRNA-microarray analysis to investigate the root-miRNA profiles of two cultivars, Bezostaja (sensitive) and Seri-82 (tolerant). A total of 44 differentially regulated miRNAs were identified in the 8 x 15K array containing 11 862 plant miRNAs available in the database. Sixteen novel salt-responsive miRNAs were determined in wheat for the first time. The expression of three miRNAs (hvu-miR5049a, ppt-miR1074 and osa-miR444b.2) was up-regulated more than 260-fold in cv. Bezostaja upon salt stress. The target-gene analyses showed that several salt-stress-responsive miRNAs regulate mainly transcription factors such as bHLH135-like, AP2/ERBP, MADS-box and transporters. Gene ontology searches for 565 putative salt-stress-responsive miRNA target-genes revealed 623 processes in 10 different main topics such as metabolic process and response to stimuli. The genome-wide root miRNome study indicates salt-stress-responsive wheat miRNAs and the possible mechanisms behind the tolerance.