To identify potential and useful markers able to discriminate promising lines of durum wheat (Triticum turgidum L. var durum) tolerant to salt and drought stresses, nucleotide sequences of Dehydration-Responsive-Element Binding Factor (DREB) genes were used to design primers probed with High Resolution Melting technology for the identification of allelic variants. DREB1, DREB2, DREB3, DREB4 and DREB5 conserved regions corresponding to EREBP/AP2 domain and containing the conserved core sequence (5'-TACCGACAT-3'), the protein site directly involved in DNA recognition, were analyzed. The validated primers were probed on four lines of durum wheat differentially tolerant to salt and drought stresses treated with solutions containing different salt concentrations. Some SNPs mutations were identified in the highly tolerant durum cultivar Jennah Khetifa treated with the maximum salt concentration (1.5 M). The SNPs mutations identified were non-synonymous (nsSNPs) causing changes in peptide sequences. These concerned amino acid residues directly involved in the maintenance of protein geometry, the recognition of the specific cis-element, and the contacts between the protein and DNA. A validation of the found SNPs was carried out by analyzing the regressions between DREBs SNPs allelic variants and some morpho-physiological characters in a RIL population, deriving from a cross between the two durum wheat genotypes utilized for SNPs detection, grown under contrasting environments. Several phenotypical characters have been assessed in the progeny across all the localities evaluating the different performances under different stress levels and related with SNPs occurrence. Significant relations between SNPs variants and morpho-physiological characteristics were found in the progeny growth in very severe drought environments, suggesting a role of the identified SNPs in conferring a superior capability to adverse stress conditions and, at the same time, the key role of these genes in empowering salt tolerance.