Objective The purpose of this study was to gain a further understanding of the relationship between miR-152 and human leukocyte antigen (HLA)-G in human trophoblast cell line (JEG-3). Study Design The JEG-3 cells were transfected with pre–miR-152. The effect of the overexpressed miR-152 on HLA-G expression, trophoblast invasion, and natural killer (NK) cell–mediated cytolysis were assessed by reverse-transcription polymerase chain reaction (RT-PCR) and Western blot analysis, transwell invasion assay, and NK cell cytotoxicity assay, respectively. Results The miR-152 repressed HLA-G expression but exerted no effect on JEG-3 cell invasion, and overexpression of miR-152 led to increased NK cell–mediated cytolysis in JEG-3 cells. Conclusion The data indicate that miR-152 may function as an immune system enhancer through up-regulating NK cell–mediated cytolysis of host cells.