Capsaicin (8-methyl-N-vanillyl-6-nonenamide), the major pungent ingredient of red pepper, has been reported to possess anti-carcinogenic and anti-mutagenic activities. In this study, the effects of capsaicin on human glioblastoma A172 cells were investigated. Treatment of A172 cells with capsaicin inhibited cell growth and induced apoptosis through down-regulation of Bcl-2 and activation of caspase-3. Interestingly, synergistic induction of morphological alternation was observed when A172 cells were treated with capsaicin. A double immunostaining analysis indicated that capsaicin stimulated terminal differentiation predominantly to astrocyte-like cells. Moreover, capsaicin increased the transcription levels of glial fibrillary acidic protein (GFAP) and neuronal microtubule-associated protein 2ab (MAP2ab). These results demonstrated that capsaicin inhibits A172 cell growth through apoptosis and terminal differentiation. Consequently, this research may provide further support for capsaicin-based anti-tumor therapies and consideration should be given to developing capsaicin for use in chemotherapy for malignant human glioblastoma.