Abstract: OBJECTIVE To investigate the effect of temozolomide(TMZ) hexyl easter(TMZ-HE) on the proliferation and apoptosis of brain glioma T98G cells in vitro compared with TMZ, and then illustrate the mechanism. METHODS Methyl thiazolyl tetrazolium (MTT) assay and colony formation assay was used to compare the effect of TMZ and TMZ-HE on cell proliferation. Cell apoptosis rate and cell cycle induced by TMZ and TMZ-HE were analyzed by flow cytometry. Western blot was used to detect the expression of Bax, Bcl-2, O⁶-methyl-oguanine-DNA-methyltransferase(MGMT), γH2AX after treated with TMZ and TMZ-HE. RESULTS TMZ-HE obviously suppressed the cell proliferation in a concentration and time-dependent manner compared with TMZ, and it was more obvious in long-term effect; TMZ-HE induced more cellular apoptosis of the T98G cells than TMZ; TMZ-HE induced a distinct G2 arrest in T98G cell; TMZ-HE induced apoptosis by increasing the ratio of Bax/Bcl-2, TMZ-HE consumed MGMT more significant than TMZ, and produced more DNA damage. CONCLUSION TMZ-HE has an advantage over the effect of anti-proliferative and induced apoptosis than TMZ, and the ability of TMZ-HE to consume MGMT and DNA damage is improved.