Increasing evidence confirms that aberrant miRNA expression contributes to breast cancer (BC) development and progression. However, the roles of different miRNAs in BC remain to be explored. In the present study, we demonstrated that miR-1297 expression was increased in BC tissues and cell lines. Our clinical analysis revealed that the upregulated miR-1297 expression was significantly correlated with poor prognostic features including advanced TNM stage and larger tumor size. Moreover, we found that miR-1297 was a novel independent prognostic marker for predicting 5-year survival of BC patients. The ectopic overexpression of miR-1297 promoted cell proliferation, cell cycle progression and inhibited apoptosis while miR-1297 knockdown reversed the effect. In addition, miR-1297 modulated PTEN by directly binding to its 3'-UTR, resulting in activation of AKT signaling. In clinical samples of BC, miR-1297 inversely correlated with PTEN, which was downregulated in BC. Alternation of PTEN expression or AKT inhibitor at least partially abolished the biological effects of miR-1297 on BC cells. In conclusion, our results indicated that miR-1297 functioned as an oncogene in regulating the proliferation, cell cycle and apoptosis of BC via targeting PTEN/PI3K/AKT signaling, and may represent a novel potential therapeutic target and prognostic marker for BC.