Objective To investigate the effect of matrix metalloproteinase 14 (MMP14) on the proliferation and migration of MDA-MB-231 human breast cancer cells treated with leptin. Methods MDA-MB-231 breast cancer cells were randomly divided into control group and (50, 100, 200, 400) ng/mL leptin treated groups. Real-time fluorescence quantitative PCR and Western blot were used to detect the expressions of MMP14 mRNA and protein in cancer cells. The MMP14 of MDA-MB-231 cells and leptin receptor genes were silenced and the silenced cells were stimulated with different concentrations of leptin, then cell proliferation was detected by MTT assay, cell migration was detected by scratch assay, and MMP14 protein expression was detected by Western blot. Results Compared with those in the control group, the mRNA and protein expressions of MMP14 increased in a dose-dependent manner in leptin treated groups. After knockdown of MMP14 and leptin receptor genes, the promoting effect of leptin on the proliferation and migration of MDA-MB-231 cells and the expression of MMP14 protein were weakened. Conclusion Leptin up-regulates the expression of MMP14 in MDA-MB-231 cells and promotes cell proliferation and migration.