In our study, we found miR-149-5p decreased after co-culture, and could increase HCC cells invasion and migration by targeting 3'UTR of MMP9, what's more, by using HCC-oemiR-149-5p cells in in vitro and in vivo experiment could reverse M2 macrophages' function to HCC cells, which strongly proved miR-149-5p's negative roles on regulating tumor progression. This evidence concerns the gene MMP9 and hepatocellular carcinoma.