Objective: To explore the expression level of tumor suppressor gene FoxO3 in the recurrent glioblastoma tissues and its potential function in temozolomide(TMZ) resistance. Methods: The expression level of FoxO3 mRNA and protein were detected and compared in primary and recurrent glioblastoma tissues via microarray, qPCT and Western blot. And then to explore the potential mechanism of FoxO3 mediated in TMZ resistance by screening its target using a microarray. Results: The expression level of FoxO3 mRNA and protein is decreased both in recurrent glioblastoma tissues and TMZ- resistance glioblastoma cell lines. Overexpression of FoxO3 could sensitize glioblastoma cells to TMZ via modulating the expression of REV3L. Conclusion: The expression level of FoxO3 is decreased in recurrent glioblastoma tissues, which might play a pivotal role in chemotherapy-resistance. Overexpression of FoxO3 could sensitize glioblastoma cells to TMZ via suppressing the expression of REV3L.