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Since the failure of traditional therapy, gene therapy using functional DNA sequence and small RNA/DNA molecules (oligonucleotide) has become a promising avenue for cancer treatment. The discovery of RNA molecules has impelled researchers to investigate small regulatory RNA from various natural and artificial sources and determine a cogent target for controlling tumor progression. Small regulatory RNAs are used for therapeutic silencing of oncogenes and aberrant DNA repair response genes. Despite their advantages, therapies based on small RNAs exhibit limitations in terms of stability of therapeutic drugs, precision-based delivery in tissues, precision-based intercellular and intracellular targeting, and tumor heterogeneity-based responses. In this study, we summarize the potential and drawbacks of small RNAs in nucleic acid therapeutics for cancer.