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Grain size and shape are important determinants of grain weight and yield in rice. Here, we report a new major quantitative trait locus (QTL), q TGW3 , that controls grain size and weight in rice. This locus, q TGW3 , encodes OsSK41 (also known as OsGSK5), a member of the GLYCOGEN SYNTHASE KINASE 3/SHAGGY-like family. Rice near-isogenic lines carrying the loss-of-function allele of Os SK41 have increased grain length and weight. We demonstrate that OsSK41 interacts with and phosphorylates AUXIN RESPONSE FACTOR 4 (OsARF4). Co-expression of Os SK41 with Os ARF4 increases the accumulation of OsARF4 in rice protoplasts. Loss of function of Os ARF4 results in larger rice grains. RNA-sequencing analysis suggests that Os ARF4 and Os SK41 repress the expression of a common set of downstream genes, including some auxin-responsive genes, during rice grain development. The loss-of-function form of Os SK41 at q TGW3 represents a rare allele that has not been extensively utilized in rice breeding. Suppression of Os SK41 function by either targeted gene editing or QTL pyramiding enhances rice grain size and weight. Thus, our study reveals the important role of OsSK41 in rice grain development and provides new candidate genes for genetic improvement of grain yield in rice and perhaps in other cereal crops. [ABSTRACT FROM AUTHOR]