Collectively, our study demonstrates that GAS5 enhances the efficacy of tamoxifen in the treatment of breast cancer and could be a novel prognostic biomarker. Tamoxifen is a frequently used drug for hormonal therapy in patients with breast cancer, however, development of resistance to tamoxifen remains a serious clinical problem.Kaplan-Meier survival analysis was used to analyze the relationship between the expression of GAS5 and survival rate. P < 0.05 indicates a significant difference. Moreover, GAS5 increased sensitivity of breast cancer cells to tamoxifen by serving as a molecular sponge for miR-222, contributing to suppression of phosphatase and tensin homologs (PTEN) (one endogenous target of miR-222).