To investigate the effects of micro ribonucleic acid (miR)-125a-5p on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells and its possible mechanism. With NSCLC A549 cells as the experimental research objects, transfection reagent was employed to transfect miR-125a-5p NC group, miR-125a-5p mimic group and miR-125a-5p siRNA group into A549 cells. qRT-PCR and cloning assays were conducted to detect the level of miR125a-5p in A549 cells and the effect of miR125a-5p on the proliferation of A549 cells. The effect of miR-125a-5p on apoptosis of A549 cells was detected via FCM. Additionally, the effects of miR-125a-5p on the mRNA and protein expressions of PI3K and AKT and the expressions of MMP-2 and MMP-9 in A549 cells were determined through qRT-PCR, Western blotting and immunohistochemistry, respectively. Compared with those in miR-125a-5p NC group, the proliferation ability of A549 cells was improved, their apoptosis rate was significantly decreased, and the mRNA and protein levels of PI3K and AKT and the levels of MMP-2 and MMP-9 in A549 cells were increased in miR-125a-5p siRNA group, whereas they showed totally opposite tendencies in miR-125a-5p mimic group. miR-125a-5p overexpression can hinder A549 cell growth, boost apoptosis, and reduce MMP-2 and MMP-9 levels via the PI3K/AKT/MMP pathway.