Glioblastoma (GBM), a highly aggressive brain tumor, thrives in hypoxic environments. Tumor-derived exosomes are key drivers of glioma progression, facilitating tumor growth, immune evasion, angiogenesis, and therapy resistance. Acrolein, a toxic byproduct produced under hypoxic conditions, causes DNA damage, inflammation, mitochondrial dysfunction, and potentiates oxidative stress. Elevated acrolein levels and associated DNA damage are linked to poor GBM prognosis. This study aims to uncover the role of acrolein in GBM progression through exosome-mediated pathways and the associated molecular mechanisms. We found that acrolein production under hypoxia promotes GBM cell malignant behavior, such as migration and spheroid formation, by downregulating neural cell adhesion molecule 1 (NCAM1) via autocrine and paracrine signaling of miR-30a-5p. Inhibiting the miR-30a-5p/NCAM1 axis reverses the tumor-promoting effects of acrolein treatment. Analysis of tumor samples from GL261 tumor-bearing mice and glioma patients showed that decreased NCAM1 levels in glioma tissues correlate with elevated acrolein expression. In patient GBM samples, lower NCAM1 levels are associated with a worse prognosis. This study suggests that targeting the miR-30a-5p/NCAM1 axis could be a potential therapeutic strategy for GBM.