Sorghum is not only an important cereal crop but also a biofuel crop. The sorghum brown midrib mutant 6 (bmr6) has a reduced lignin content in the cell walls and vascular tissues, which could potentially be advantageous for cellulosic biofuel production. Meanwhile, both dry matter yield and plant height were decreased in the bmr6 mutant. To identify genes affected in the mutant, differential gene expression analysis was performed for bmr6 and the wild type. As a result, a total of 1,052 differentially expressed genes were detected between the two samples, of which 166 genes were downregulated and 886 genes were upregulated. Five hundred seventy-nine of the 1,052 differentially expressed genes could be assigned to 154 documented pathways. These pathways mainly included primary and secondary metabolism. Therefore, mutation of the bmr6 gene, which impaired the biosynthesis of lignin, ultimately affected the expression of these genes associated with the growth and development of sorghum. Except for the bmr6 gene, 11 key enzyme genes of monolignols biosynthesis were upregulated. Promoter analysis identified that these genes have common MYB sites. It revealed that a feedback mechanism existed in the pathway and a MYB1 transcription factor (Sb02g031190) could associate with the upregulation of these genes in sorghum. In this study, we investigated gene expressions at a global level in sorghum bmr6 mutant and provided valuable insights into the mechanisms of lignin biosynthesis.