The most familiar action of mode performed by RNA regulation is the posttranscriptional gene silencing in the cytoplasm. The discovery of siRNA-directed DNA methylation in nucleus has proved that siRNA can induce transcriptional gene silencing by siRNA-guided genome modifications. DNA methylation was once predicted to be an epigenetic mechanism of tumor biogenesis. It is well known that the abnormal inhibition of tumor-suppressor genes is associated with DNA de novo methylation in the gene promoter region. Potential molecular mechanisms of tumour-suppressor gene silencing was analized, the principle of siRNA-directed transcriptional suppression was explored, and the possible relationship between them was clarified. The detailed study on the relationship between DNA methylation and RNA interference will be beneficial to better understand tumor biology and epigenetics, and also provide new therapeutic strategies for the prevention and treatment of cancer.