A novel salt overly-sensitive 2 (SOS2) interaction protein was identified by yeast two hybrid (Y2H) library and was referred to as SOS2 interaction protein 1 (SIP1). SIP1 belongs to a plant-specific protein family, which contains a conserved domain that corresponds to a putative N-acetyltransferase. The members of this family are tolerant to heavy metals and oxidative stress. Here, SIP1 was identified as a salt-responsive gene. The sos2 x sip1-1 double mutant was more sensitive than the sos2 single mutant upon salt stress, whereas the overexpression of SIP1 gene enhanced the plant salt tolerance, suggesting that SIP1 was involved in plant salt tolerance. We also found that SIP1 increasingly accumulated in response to salt stress, and this accumulation was inhibited in the sos2 mutant background. This finding suggests that the function of SIP1 upon salt stress was dependent on SOS2 protein. Further investigation suggested that SIP1 improved Arabidopsis tolerance to salt stress by reducing the ROS accumulation. Taken together, these findings reveal a novel function of SIP1 in adjusting Arabidopsis adaptation to salt stress.