Melatonin is a pleiotropic signaling molecule, which, besides being involved in multiple growth and developmental processes, also mediates environmental stress responses. However, whether and how endogenous melatonin is involved in salt response has not been determined. In this study, we elucidated the involvement of endogenous melatonin in salt response by investigatiing the impact of salt stress on a double mutant of Arabidopsis (snat1snat2)defective in melatonin biosynthesis genes SNAT1 and SNAT2. This mutant was found to exhibit salt sensitivity, manifested by unhealthy growth, ion imbalance and ROS accumulation under salt stress. Transcriptomic profiles of snat1snat2 revealed that the expression of a large number of salt-responsive genes was affected by SNAT defect, and these genes were closely related to the synthesis of auxin and several signaling pathways. In addition, the salt-sensitive growth phenotype of snat1snat2 was alleviated by the application of exogenous auxin. Our results show that endogenous melatonin may be essential for plant salt tolerance, a function that could be correlated with diverse activity in mediating auxin signaling.