Micro-RNAs (miRNAs) are small RNA molecules that regulate the expression of genes involved in development, growth, proliferation and apoptosis. In cancer several miRNAs have been functionally classified as oncogenes or tumour suppressers or act to regulate transcription factors, like nuclear factor kappa B and NF-E2–related factor 2, in cancers such as leukaemia, breast and colorectal. Therefore, it has been proposed that manipulating miRNA regulation may be a novel avenue for developing efficient therapies against cancer. In this issue, Li and colleagues describe a novel way of targeting miRNA, by using a naturally occurring anti-cancer compound found in mistletoe which they showed to down-regulate miR-135a&b, which target the 3' untranslated region of adenomatous polyposis coli gene, the inactivation of which is a major initiating event in colorectal tumourigenesis. This commentary aims to discuss the regulatory mechanisms of miRNA synthesis and the potential outcomes for using naturally occurring compounds antioxidants or cellular antioxidant pathways to target miRNA for therapeutic intervention.