As sessile organisms, plants are always exposed to various abiotic stresses, and therefore, they have developed defense mechanisms against abiotic stresses. Ubiquitin-mediated proteasomal degradation is an important mechanism that regulates the level of proteins in plants. The present study describes Oryza sativa salt-induced RING finger protein 3 (OsSIRP3), a functional RING E3 ligase, that is possibly involved in salt-stress response. The transcript of OsSIRP3 gene was highly expressed in whole rice samples, such as root and shoot, after exposure to high salinity stress. Furthermore, in vitro ubiquitination assay demonstrated that OsSIRP3 has E3 ligase activity due to RING H2 domain. The results revealed the interaction of OsSIRP3 with both salt-induced and non-induced proteins, leading to their degradation via ubiquitin (Ub)/26S proteasome-mediated system. Overexpression of OsSIRP3 in Arabidopsis resulted in hypersensitivity phenotypes under salinity stress during seed germination and root growth. These findings suggest that OsSIRP3 negatively regulates salinity stress response by modulating the level of its target proteins.