Glioblastoma multiforme (GBM) is the most malignant neuroepithelial primary brain tumor and its mean survival time is 15 months after diagnosis. This study undertook to investigate the genome-wide and transcriptome-wide analyses of human high mobility group box (HMG-box) TF (transcript factor) families / HOX, TOX, FOX, HMG and SOX gene families, and their relationships to GBM. According to the TCGA-GBM profile analysis, differentially expressed HOX, FOX, HMG and SOX gene families (62 DEmRNA) were found in this study. We also analyzed DEmRNA (HMG-box related genes) co-expressed eight DElncRNA in GBM, and constructed a ceRNA network analysis as well. We constructed 50 DElncRNA-DEmiRNA-DEmRNA (HMG-box related genes) pairs between GBM and normal tissues. Then, risk genes SOX6 and SOX21 expression were correlated with immune infiltration levels in GBM. SOX6 also had a strong association with MAPT, GSK3B, FYN and DPYSL4, suggesting that they might be functional members in GBM.