The mature microRNA hsa-miR-125a-3p is derived from the 3' end of pre-miR-125a. Here, we reported that hsa-miR-125a-3p suppressed proliferation and induced apoptosis in A549 cells. In addition, wild-type p53 mRNA and protein expression was increased by hsa-miR-125a-3p over-expression. Moreover, blocking wild-type p53 attenuated the effect of hsa-miR-125a-3p on apoptosis but could not restore completely. In p53-deficient cell line H1299, hsa-miR-125a-3p still induced apoptosis. Taken together, these data suggest that hsa-miR-125a-3p induces apoptosis not only via the p53 pathway in human lung cancer cells. These results provide new insight into the roles of the miR-125a family in lung cancer.