Objective: To investigate the effect of miR-150-5p on migration and invasion in hepatocellular carcinoma (HCC) cells and the mechanism. Methods: The miR-150-5p expression in normal hepatic cells and HCC HepG2 cells was determined by real-time PCR. Then, the HepG2 cells were divided into two groups to transfect with miR-150-5p (miR-150-5p group) or scramble sequences (control group), respectively. After transfection, the cell migration and invasion abilities were measured by wound healing assay and Transwell invasion assay, and the protein expressions of matrix metalloproteinase 2 (MMP2) and 9 (MMP9) were examined by Western blot, respectively. Results: The expression level of miR-150-5p in HepG2 cells was significantly reduced, and was 26% of that in normal hepatic cells (P<0.01). After transfection, the miR-150-5p expression level in miR-150-5p group was significantly increased, which was 9.53 times of that in control group (P<0.001). In miR-150-5p group compared with control group, the healing rate of the scratch wound (54.63% vs. 87.51%, P<0.01) and number of invaded cells (138 vs. 452, P<0.01) were all significantly decreased. The protein expression levels of MMP2 and MMP9 (0.78 vs. 1.75; 0.82 vs. 1.85) were all significantly decreased (both P<0.05). Conclusion: The miR-150-5p expression is decreased in HCC cells, and up-regulation of miR-150-5p expression can inhibit the migration and invasion of HCC cells and the mechanism may be associated with its suppressing MMP2 and MMP9 expressions.