SIMILAR TO RCD-ONEs (SROs) comprise a small plant-specific gene family which play important roles in regulating numerous growth and developmental processes and responses to environmental stresses. However, knowledge of SROs in sesame (Sesamum indicum L.) is limited. In this study, four SRO genes were identified in the sesame genome. Phylogenetic analysis showed that 64 SROs from 10 plant species were divided into two groups (Group I and II). Transcriptome data revealed different expression patterns of SiSROs over various tissues. Expression analysis showed that Group II SROs, especially SiSRO2b, exhibited a stronger response to various abiotic stresses and phytohormones than those in Group I, implying their crucial roles in response to environmental stimulus and hormone signals. In addition, the co-expression network and protein-protein interaction network indicated that SiSROs are associated with a wide range of stress responses. Moreover, transgenic yeast harboring SiSRO2b showed improved tolerance to salt, osmotic and oxidative stress, indicating SiSRO2b could confer multiple tolerances to transgenic yeast. Taken together, this study not only lays a foundation for further functional dissection of the SiSRO gene family, but also provides valuable gene candidates for genetic improvement of abiotic stress tolerance in sesame.