Grain size, which encompasses length, width, and thickness, is a critical agricultural trait that influences both grain yield and quality in rice. Although numerous grain size regulators have been identified, the molecular mechanisms governing grain size and the lignin content remain largely elusive. In this study, we cloned and characterized GRAIN LENGTH AND GRAIN WIDTH 10 (GLGW10), a regulator of grain size in rice. Loss-of-function mutations in GLGW10 result in reduced grain size. GLGW10 encodes an evolutionarily conserved protein, the function of which has not been previously characterized in higher plants. Biochemical assays reveal that GLGW10 may interact with the transcription factor OsMYB108, which acts as a negative regulator of the lignin content. Knockout of OsMYB108 leads to longer and slender grain size, accompanied by increased lignin content, indicating that OsMYB108 negatively regulates both grain size and lignin content. Analysis of natural variations and haplotypes in GLGW10 reveals an association with grain size, suggesting an artificial selection on GLGW10 during rice domestication. In summary, our findings identify regulators of grain size and elucidate potential mechanisms linking grain size and lignin metabolism in rice, thereby providing essential insights for improving crop yields.