Arsenic trioxide (As"2O"3) has considerable efficacy in treating solid tumors with induction of apoptosis with largely unknown mechanisms. Posttranslational processing of proteins by glycosylation could have multiple regulating roles in the process of apoptosis. Here, we found that the expression of @b1,6-linked GlcNAc-bearing N-glycans on cell surface protein was gradually decreased after induction of apoptosis by As"2O"3-treatment. And, As"2O"3 significantly decreased the protein expression level of @b1,4GalT V, which effectively galactosylates the @b1,6-GlcNAc branch of N-glycans and functions as a positive regulator in glioma development. Furthermore, interfering with the expression of @b1,4GalT V in human glioma cell markedly promoted As"2O"3-induced cell apoptosis and @b1,4GalT V overexpression significantly reduced As"2O"3-induced glioma cell apoptosis. Taken together, our results suggested that down-regulation of @b1,4GalT V expression plays an important role in As"2O"3-induced apoptosis, providing a new mechanism of As"2O"3-induced cell apoptosis and indicating that inhibitors of @b1,4GalT V may enhance the therapeutic efficiency of As"2O"3 for malignant glioma.