MicroRNAs are small endogenous noncoding RNAs, which modulate target gene expression by binding with target mRNA sequences in the 3'untranslated region (UTR) with an imperfect complementarity that inhibits the mRNA translation. Many microRNAs have been reported to function as tumor oncogenes or anti-oncogenes. Recently, more and more microRNAs have been reported to contribute to a tumor's invasive potential. Here, we show that microRNA-10b (miR-10b) was over-expressed in glioma samples and directly associated with the glioma's pathological grade and malignancy. We also found that miR-10b induced glioma cell invasion by modulating tumor invasion factors MMP-14 and uPAR expression via the direct target HOXD10. The miR-10b/HOXD10/MMP-14/uPAR signaling pathway might contribute to the invasion of glioma. Accordingly, glioma cells lost their invasive ability when treated with specific antisense oligonucleotides (miR-10b inhibitors), suggesting that miR-10b could be used as a new bio-target to cure glioma.