Objective To explore the expression level and clinical significance of claudin 7 （CLDN7） in glioblastoma （GBM） tissues. Methods The gene expression data related to GBM and normal brain tissues were obtained from The Cancer Genome Atlas （TCGA） and Genotype-Tissue Expression （GTEx） databases， respectively， and the correlation between CLDN7 and clinical data was analyzed by comparing the differences in CLDN7 gene expression within the two groups with the help of R software. The prognosis of CLDN7 in patients with human GBM was assessed using Kaplan-Meier survival analysis， receiver operating characteristic （ROC） curve analysis， and nomogram. STRING database was used to evaluate the interacting genes and signaling pathways of CLDN7. Results A total of 689 normal samples and 1 157 GBM samples were collected. The expression of CLDN7 in GBM tissue was higher than that in normal brain tissue ［1.029 （0.642，1.546）］ vs. ［0.475 （0.275， 0.740）］， and the difference was statistically significant （Z=-20.004， P＜ 0.001）. The expression level of CLDN7 in patients aged ＞ 60 years， with high WHO pathological grade and 1p/19q non co-deletion was higher than that in patients aged ≤ 60 years， with low WHO pathological grade and 1p/19q co-deletion， and the difference was statistically significant （Z=-20.683，154.210，-2.699， all P ＜ 0.001）. Survival analysis showed that CLDN7 high expression group had a shorter survival period compared to the low expression group， and the difference was statistically significant （P ＜ 0.001）. ROC curve showed that the area under the curve for diagnosing glioblastoma patients with CLDN7 was 0.776. Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis revealed that proteins associated with CLDN7 were mainly involved in signaling pathways such as tight junctions， adhesion links， cell adhesion molecules， and leukocyte transendothelial migration. Conclusions CLDN7 is highly expressed in GBM tissues and may be an indicator of diagnosis of GBM and poor prognosis.