ABSTRACT: Plants adapt to abiotic stresses by complex mechanisms involving various stress-responsive genes. Here, we identified a DEAD-box RNA helicase (RH) gene, AtRH17, in Arabidopsis, involved in salt-stress responses using activation tagging, a useful technique for isolating novel stress-responsive genes. AT895, an activation tagging line, was more tolerant than wild type (WT) under NaCl treatment during germination and seedling development, and AtRH17 was activated in AT895. AtRH17 possesses nine well-conserved motifs of DEAD-box RHs, consisting of motifs Q, I, Ia, Ib, and II-VI. Although at least 12 orthologs of AtRH17 have been found in various plant species, no paralog occurs in Arabidopsis. AtRH17 protein is subcellularily localized in the nucleus. AtRH17-overexpressing transgenic plants (OXs) were more tolerant to high concentrations of NaCl and LiCl compared with WT, but no differences from WT were detected among seedlings exposed to mannitol and freezing treatments. Moreover, in the mature plant stage, AtRH17 OXs were also more tolerant to NaCl than WT, but not to drought, suggesting that AtRH17 is involved specifically in the salt-stress response. Notably, transcriptions of well-known abscisic acid (ABA)-dependent and ABA-independent stress-response genes were similar or lower in AtRH17 OXs than WT under salt-stress treatments. Taken together, our findings suggest that AtRH17, a nuclear DEAD-box RH protein, is involved in salt-stress tolerance, and that its overexpression confers salt-stress tolerance via a pathway other than the well-known ABA-dependent and ABA-independent pathways.