The Arabidopsis FOUR LIPS (AtFLP), an R2R3 MYB transcription factor, acts as an important stomatal development regulator. Only one orthologue protein of AtFLP, Oryza sativa FLP (OsFLP), was identified in rice. However, the function of OsFLP is largely unknown. In this study, we conducted RNA-seq and ChIP-seq to investigate the potential role of OsFLP in rice. Our results reveal that OsFLP is probably a multiple functional regulator involved in many biological processes in growth development and stress responses in rice. However, we mainly focus on the role of OsFLP in salt stress response. Consistently, phenotypic analysis under salt stress conditions showed that osflp exhibited significant sensitivity to salt stress, while OsFLP over-expression lines displayed obvious salt tolerance. Additionally, Yeast one-hybrid assay and electrophoretic mobility shift assay (EMSA) showed that OsFLP directly bound to the promoter region of Oryza sativa B-type Cyclin-Dependent Kinase 1;1 (OsCDKB1;1), and the expression of OsCDKB1;1 was repressed in osflp. Disturbing the expression of OsCDKB1;1 remarkably enhanced the tolerance to salt stress. Taken together, our findings reveal a crucial function of OsFLP regulating OsCDKB1;1 in salt tolerance and largely extend the knowledge about the role of OsFLP in rice.