RNA interference (RNAi) is a phenomenon of sequence-specific gene silencing and its discovery led to wide applications. Short interfering RNA (siRNA), which induces RNAi, has been experimentally introduced as a cancer therapy and is expected to be developed as a nucleic acid-based medicine. Potential success of siRNA cancer therapies depends on selection of appropriate gene targets and candidate targets include genes associated with cell proliferation, metastasis, angiogenesis, and drug resistance. In vivo systemic delivery of siRNA-based therapeutics to tumour tissues is challenging and the major limitations of siRNA therapeutic use are its degradation by serum nucleases, poor cellular uptake and rapid renal clearance following systemic administration. Several siRNA-based therapeutics are already in clinical trials. Further development of anti-cancer therapeutic siRNAs depends on development of nanocarriers, nuclease-resistant chemically modified siRNAs and variety of synthetic or natural lipids and polymers to systemically deliver siRNA. Here, we review potential approaches for delivery of RNAi based therapeutic in cancer therapy, results of current studies and clinical trials which demonstrate that the use of targeted siRNA offers promising strategies for cancer therapies.