microRNAs play an important roles in cellgrowth, differentiation, proliferationand apoptosis. They can function either as tumor suppressors or oncogenes. We found that the overexpression of miR- 192inhibited cell proliferation inA549, H460 and 95D cells, and inhibited tumorigenesis ina nude mouse model. Both caspase-7 and the PARP protein were activated by the overexpression of miR- 192, thus suggesting that miR- 192 induces cell apoptosisthrough the caspase pathway. Further studies showed that retinoblastoma 1(RB1) is a direct target of miR- 192. Over-expression of miR- 192decreased RB1 mRNA and protein levels and repressed RB1-3'-UTR reporter activity. Knockdown of RB1 using siRNA resulted ina similar cellmorphology as that observed for overexpression of miR- 192. Additionally, RB1-siRNA treatment inhibited cell proliferationand induced cell apoptosis in lung cancer cells. Analysis of miRNA expression inclinical samples showed that miR- 192is significantly downregulated in lung cancertissues compared to adjacent non-cancerous lungtissues. Inconclusion, our results demonstrate that miR- 192is a tumor suppressor that can target the RB1 gene to inhibit cell proliferationand induce cell apoptosis in lung cancer cells. Furthermore, miR- 192was expressed at low levels in lung cancersamples, indicating that it might be a promising therapeutic target for lung cancertreatment.