High-salt stress severely inhibits plant growth and development, leading to a significant reduction in rice yield. Although significant progress has been made in understanding the functions of plant MAP4Ks in stress responses, the role of rice MAP4Ks in abiotic stress, particularly salt tolerance, remains largely unexplored, highlighting a critical knowledge gap. Here, we identify OsMAP4K6 as a positive regulator of salt stress tolerance in rice, a role previously unreported for this gene family in monocot plants. We demonstrate that OsMAP4K6 modulates root Na⁺ flux and maintains Na⁺/K⁺ homeostasis under salt stress. Furthermore, we uncover a unique regulatory mechanism by which OsMAP4K6 directly interacts with and phosphorylates OsMKK6 at Ser13, and this Ser13 phosphorylation is essential for enhancing the activation of OsMKK6 under salt stress. Our genetic evidence reveals that OsMKK6 and OsMAP4K6 play similar roles in salt stress tolerance in rice. Our findings not only establish OsMAP4K6 as a key player in rice salt tolerance but also reveal a novel, direct regulatory pathway linking a MAP4K to a component of the MAPK cascade, providing new mechanistic insight into salt stress adaptation in plants.