MicroRNAs (miRNAs) are small single-strand non-coding endogenous RNAs that regulate gene expression by multiple mechanisms. Recent evidence suggests that miRNAs are critically involved in the pathogenesis, evolution, and progression of cancer. The miRNAs are also crucial for the regulation of cancer stem cells (CSCs). In addition, miRNAs are known to control the processes of Epithelial-to-Mesenchymal Transition (EMT) of cancer cells. This evidence suggests that miRNAs could serve as targets in cancer treatment, and as such manipulating miRNAs could be useful for the killing CSCs or reversal of EMT phenotype of cancer cells. Hence, targeting miRNAs, which are deregulated in cancer, could be a promising strategy for cancer therapy. Recently, the regulation of miRNAs by natural, nontoxic chemopreventive agents including curcumin, resveratrol, isoflavones, (-)-epigallocatechin-3-gallate (EGCG), lycopene, 3,3'- diindolylmethane (DIM), and indole-3-carbinol (I3C) has been described. Therefore, natural agents could inhibit cancer progression, increase drug sensitivity, reverse EMT, and prevent metastasis though modulation of miRNAs, which will provide a newer therapeutic approach for cancer treatment especially when combined with conventional therapeutics.