Conclusions: Telbivudine is a cost-effective alternative to entecavir particularly when its cost is low in Hong Kong. H. Tang 1 , G.L. Zhang 1 , Y.X. Li 1 , R.Q. Tian 1 , M. Liu 1 , X. Li 1 1 Tianjin Life Science Research Center, Tianjin Medical University, Tianjin 300070, China MicroRNAs (miRNAs) are single-stranded noncoding RNAs of 18 to 25 nucleotides that play critical roles in a wide spectrum of biological processes. We investigated whether the miRNAs-silencing machinery influences HBV replication or antigen expression. On the basis of ELISA and MTT, the effect of 328 miRNAs on the HBsAg expression and cell proliferation was examined. Three microRNAs efficiently inhibited HBsAg expression without significant effect on the proliferation of HepG2 2.2.15 cells compared to LacZ control. Subsequently, bioinformatics analysis were used to predict targets for the three miRNAs, and the prediction results were conformed by cDNA microarray analysis. The target region in HBV genome and the 3'UTR region of one cellular gene were identified by fluorescent reporter assay, semi-quantitative RT-PCR and western blot. The results demontrated that miRNA may play an important role in replication and gene expression of HBV.