The mutation of cancer represents a high heterogeneity characteristic, setting a big obstacle in the mechanism study of it. In this study, we explored the distributions of mutated genes in pathways in glioblastoma multiforme (GBM), and constructed networks of co-mutated pathway pairs under the false discovery rate (FDR) control. By comparing the mutation frequencies, a total of 50 mutated genes were screened with the frequency > 3, and TP53, PTEN, and EGFR were the top 3 genes. By KEGG enrichment, 18 pathways of the mutation gene spectrum of GBM were enriched. These pathways were further studied to explore the coordination between pathways, co-mutated pathway pairs, such as mismatch repair/vascular smooth muscle contraction, mismatch repair/long-term depression, mismatch repair/dopaminergic synapse, and TGF-beta signaling pathway/retrograde endocannabinoid signaling pathway were enriched in the network under FDR < 0.01; and cell cycle/p53 signaling was a co-mutated pathway pairs in the network under FDR < 0.05. Meanwhile, the samples overlap levels of enriched pathways were calculated for further confirming of the co-mutated pathway model. By the co-mutated pathway analysis, the coordination mechanism of cancer can be explored, and it may provide basis for the pathogenesis and combined therapy study of cancer.