RNA activation (RNAa) is a newly discovered mechanism in which non-coding RNAs like small double-stranded RNAs (dsRNAs) or micro RNAs (miRNAs) induce sequence-speci?c gene activation by targeting promoter. Although its underlying mechanism remains unclear, we and others have demonstrated that Ago protein, RNA polymerase II (RNA Pol II) and heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) are required for RNAa. In addition, RNAa is conserved in mammalian cells. Increasing evidences indicated that dsRNAs or miRNAs can induce tumor suppressing genes expression and hold great capacity to inhibit bladder cancer cells. RNAa provides a novel method for gene manipulation and offers an exciting potential for therapeutic modality against bladder cancers. In this review, we will focus on the research advances in exploiting the mechanism of RNAa and its applications in bladder cancer therapeutics