Grain size is one of the key agronomic traits that determine grain yield in crops.However,the mechanisms underlying grain size control in crops remain elusive.Here we demonstrate that the OsMKKK10-OsMKK4-OsMAPK6 signaling pathway positively regulates grain size and weight in rice.In rice,loss of OsMKKK10 function results in small and light grains,short panicles,and semi-dwarf plants,while overexpression of constitutively active OsMKKK10 (CA-OsMKKK10) results in large and heavy grains,long panicles,and tall plants.OsMKKK10 interacts with and phosphorylates OsMKK4.We identified an OsMKK4 gain-of-function mutant (large11-1D) that produces large and heavy grains.OsMKK4A227r encoded by the large11-1D allele has stronger kinase activity than OsMKK4.Plants overexpressing a constitutively active form of OsMKK4 (OsMKK4-DD) also produce large grains.Further biochemical and genetic analyses revealed that OsMKKK10,OsMKK4,and OsMAPK6 function in a common pathway to control grain size.Taken together,our study establishes an important genetic and molecular framework for OsMKKK10-OsMKK4-OsMAPK6 cascade-mediated control of grain size and weight in rice.