Objective To explore the histopathological and molecular pathological features of isocitrate dehydrogenase （IDH） wild-type glioblastoma （GBM）. Methods From September 2021 to August 2023， 74 GBM patients with surgery at the Department of Neurosurgery， Affiliated Hospital of Hebei University were selected as the study subject. Hematoxylin-eosin staining was used to observe the pathological characteristics of tissues. Immunohistochemical staining and next-generation sequencing were used to analyze molecular pathological features. Kaplan-Meier method was used to plot survival analysis curves to analyze the relationship between patient survival and IDH1 mutations. Results Among 74 cases of GBM， males accounted for 60.81% （45/74）， and the age was （55.23±4.58） years old. Fifty-eight cases of tumors were located in the frontal lobe and 16 cases were located in the temporal lobe. The histological results of hematoxylin-eosin staining showed that 82.43% （61/74） of tumor tissues showed typical palisade necrosis， vascular proliferation， and significant tumor atypia， consistent with the typical GBM tissue morphological characteristics. The morphology of other tumor tissues matched the morphological characteristics of grade 2 or 3 astrocytoma. Immunohistochemical staining showed that all tumors were negative for IDH1 R132H staining， while Ki-67 staining showed an average positive rate of 38%. Results of the next-generation sequencing molecular pathology showed that all tissues were negative for IDH1/2， with positive amplification of epidermal growth factor receptor （EGFR） accounting for 74.32% （55/74） and telomerase reverse transcriptase （TERT） promoter region mutations accounting for 59.46% （44/74）.The proportion of pure deletion of cyclin dependent kinase inhibitor 2A/B （CDKN2A/B） was 33.78% （25/74）. The high expression level of methylation in the promoter region of O6-methylguanine-DNA methyltransferase （MGMT） accounted for 47.30% （35/74）. Conclusions GBM exhibits molecular features of IDH wild-type， with some cases accompanied by EGFR amplification， TERT promoter region mutations， CDKN2A/B homozygous deletion， and MGMT promoter region hypermethylation.