MicroRNAs (miRNAs) are endogenous small RNAs (approximately 21-25 nts) that can regulate gene expression at a post-transcriptional level. Recently a large number of miRNAs have been identified from plants and animals. In addition, it has been reported that these small RNAs can participate in cell differentiation of developmental timing. In this study, we show that microRNA-196 (miR-196) inhibits HOXB8 expression in myeloid differentiation of HL 60 cells. MiR-196 has perfect complementarity with target sequence of 3'-UTR in HOXB8 mRNA. Exogenous expressed miR-196 repressed expression of HOXB8 via cleaving mRNAs. Moreover miR-196 enhanced myeloid differentiation of HL60 cells. These results suggest that miR-196 participates in myeloid differentiation of HL60 cells via regulation of HOXB8 expression.