The small RNAs include siRNA and miRNA. SiRNA is the splicing product of exogenous dsRNA by which to keep genome stability, while miRNA are processed from endogenous genome and work as a post-transcriptional regulator for gene expression. The small RNAs act in two ways: mediate degradation of of target RNA and inhibit translation of protein. The former requires the accurate complementation between small RNA and target RNA, while the latter requires only partial complementation. Which mechanism used depends on complementation degree, but not their origins. The RNAi as a technique for down-regulating target gene expression has been widely used in functional genomic studies and hematologic studies, especially for translocation-related fusion gene, apoptosis-related gene and MDR gene in leukemia. The results show that RNAi technique not only is the powerful tool for study mechanism but also has therapeutic potentials in clinic. Some studies reveal that changes of miRNA expression exist in many hematological malignancies and relate to known oncogenes, which indicates the miRNA is involved in pathogenesis of these diseases. This article reviews the discovery and effect of RNAi and small RNAs, as well as the similarities and differences between siRNA and miRNA, and focuses on the research of small RNAs in hematological malignancies.