Many studies have reported substantial effects of miRNAs in cancer progression. These factors can act as oncogene or tumor suppressor by degrading target genes transcripts or translation inhibition [1]. Besides, miRNAs have drawn much attention as potential diagnostic markers and therapeutic targets in human cancers [2]. The literature has reported that many miRNAs are involved in breast cancer [3]. The down-regulation or up-regulation of miRNAs levels in different cancers, including breast cancer, has been strongly verified. Changes in miRNAs expression can occur due to point mutation or Single nucleotide polymorphisms (SNP), leading to an alteration in their structure and maturation processes [4, 5]. Changes in miRNAs expression profile caused by different variants in the genomic sequence can play a vital role in cancer progression [6]. Nevertheless, due to the complexity of miRNA biogenesis, targeting a specific gene by different miRNAs, the wide range of target genes, and the interaction between them, characterize the outcomes of specific SNPs in the miRNAs sequence are remarkably difficult. miR-SNPs are classified into two groups: the first group consists of SNPs in the pri- and pre-miRNA that affect its biogenesis and consequently alter the expression level of the mature miRNA, and another group is those that affect miRNA target identification [7, 8]. Numerous reports are available on miRNAs and their different genetic variants in the diagnosis and prediction of various diseases such as cancers, neurological disorders, cardiovascular disease, and type II diabetes [9, 10]. One of the most important miRNAs is miR-149, which is considered a biomarker and therapeutic target in various cancers such as head and neck, lung, stomach, breast, prostate, and renal cell carcinoma. The miR-149 targets different genes and pathways and plays a dual role in proliferation and apoptosis [11]. In some cancers such as prostate, leukemia, glioblastoma, and melanoma, mir-149 is upregulated and acts as an oncomiR, but in the hepatocellular, colorectal, lung, gastric, and breast cancers is downregulated and known as an important tumor suppressor and in some cases, its expression level has been further reduced during metastasis [11–16]. The human miR-149 has different variants, and rs2292832 is one of the most important variants, which is associated with the risk of several cancers, including lung [17], gastric and colorectal [18], head and neck, and squamous cell carcinoma [19]. Huang GL et al. Showed that the rs2292832 polymorphism contributes to the progression of esophageal cancer and significantly increases metastasis and cell proliferation [20]. However, Li L et al. observed that rs2292832 T / C polymorphism may decrease digestive cancer susceptibility [21]. In breast cancer, few studies have been performed on rs2292832 polymorphism only in the Chinese population. Since changes in miR-149 expression and its effects on tumorigenesis in breast cancer have been proved, such studies could shed light on the role of miR-149 and make it a useful therapeutic target. Therefore, this study aimed to investigate the association of rs2292832 polymorphism with breast cancer risk in a group of Iranian population, evaluate the effects of this variant on the expression of mature miRNA, and examine the viability and migration of cancer cells treated with this variant.