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Background: Tartary buckwheat has gained popularity in the food marketplace due to its abundant nutrients and high bioactive flavonoid content. However, its difficult dehulling process has severely restricted its food processing industry development. Rice-tartary buckwheat, a rare local variety, is very easily dehulled, but the cellular, physiological and molecular mechanisms responsible for this easy dehulling remains largely unclear., Results: In this study, we integrated analyses of the comparative cellular, physiological, transcriptome, and gene coexpression network to insight into the reason that rice-tartary buckwheat is easy to dehull. Compared to normal tartary buckwheat, rice-tartary buckwheat has significantly brittler and thinner hull, and thinner cell wall in hull sclerenchyma cells. Furthermore, the cellulose, hemicellulose, and lignin contents of rice-tartary buckwheat hull were significantly lower than those in all or part of the tested normal tartary buckwheat cultivars, respectively, and the significant difference in cellulose and hemicellulose contents between rice-tartary buckwheat and normal tartary buckwheat began at 10 days after pollination (DAP). Comparative transcriptome analysis identified a total of 9250 differentially expressed genes (DEGs) between the rice- and normal-tartary buckwheat hulls at four different development stages. Weighted gene coexpression network analysis (WGCNA) of all DEGs identified a key module associated with the formation of the hull difference between rice- and normal-tartary buckwheat. In this specific module, many secondary cell wall (SCW) biosynthesis regulatory and structural genes, which involved in cellulose and hemicellulose biosynthesis, were identified as hub genes and displayed coexpression. These identified hub genes of SCW biosynthesis were significantly lower expression in rice-tartary buckwheat hull than in normal tartary buckwheat at the early hull development stages. Among them, the expression of 17 SCW biosynthesis relative-hub genes were further verified by quantitative real-time polymerase chain reaction (qRT-PCR)., Conclusions: Our results showed that the lower expression of SCW biosynthesis regulatory and structural genes in rice-tartary buckwheat hull in the early development stages contributes to its easy dehulling by reducing the content of cell wall chemical components, which further effects the cell wall thickness of hull sclerenchyma cells, and hull thickness and mechanical strength.