Objective：To investigate the expression of lncRNA RP11-490M8.1 in patients with breast cancer and its roles in the proliferation of breast cancer cells. Methods：The Cancer Genome Atlas(TCGA)and the Kaplan -Meier plotter database were used to define the expression level and prognostic value of RP11-490M8.1 in breast cancer，respectively. qRT-PCR was performed to detect the expression level of RP11-490M8.1 in paired breast cancer tissues and adjacent normal tissues. CCK8 and clone formation assays were carried out to determine the effects of the overexpression or knockdown of RP11-490M8.1 on the proliferation of breast cancer cells. Results：Compared with adjacent normal tissues，RP11-490M8.1 was significantly downregulated in breast cancer tissues. Moreover， lower expression of RP11-490M8.1 was associated with the advanced clinical stage and worse overall survival(OS)(P=0.034). However，there was no correlation between RP11-490M8.1 level and the expression of estrogen receptor，progesterone receptor，human epidermal growth factor receptor-2 and age. Overexpression of RP11-490M8.1 markedly suppressed the proliferation of breast cancer cells，while knockdown of RP11-490M8.1 promoted its proliferation. Conclusion：RP11-490M8.1 acts as a tumor suppressor in breast cancer，which may serve as a potential prognostic molecule and therapeutic target for breast cancer