Objective To explore the gene expression difference of glioblastoma in different age groups through the sequencing of the transcriptome and exome. Methods Glioblastoma multiforme(GBM) data was downloaded from the Cancer Genome Atlas(TCGA), and the samples were divided into two groups. There were 78 cases in the middle and low age group not more than 60 years old, compared with the high age group of 60 years old, with a total of 76 cases. DESeq2 package was used to analyze differentially expressed genes based on gene level reads numbers. Cytoscape plug-in ClueGO was used to analyze gene function enrichment in different age groups. Results Most of the gene expression trends in the two groups were consistent between the two groups, but there were some different genes. In the middle and low age group, the differential gene was mainly related to the proliferation of neural precursor cells, while the high age group was metabolic. In the two groups, the high mutation genes were basically consistent, but the mutation rates were different. The mutation differentially genes were concentrated in the middle and low age groups. Conclusion There is a significant difference in gene expression and gene mutation between the middle and low age group and the elderly GBM group.