To date, the mechanism underlying the development of human choriocarcinomas has not been elucidated. It is hypothesized that the Sox2 protein plays a pivotal role in the proliferation and invasion capacity of tumor cells. A microRNA (miR-145) was cloned and used to study the expression of Sox2 and its regulatory effect on the proliferation and invasion capacity of the human choriocarcinoma cell line JAR. In the present study, Sox2 mRNA and protein expression decreased in JAR and JEG-3 cells following transfection with the miR-145 expression virus. Cell proliferation assays indicated that miR-145 expression affected cell cycle regulation and suppressed the proliferation of choriocarcinoma cells in vitro. In addition, xenograft experiments confirmed the suppression of tumor growth in vivo due to cell cycle arrest. Therefore, endogenous mature miR-145 expression may have an important role in the pathogenesis of human choriocarcinomas via interference with the Sox2 target gene by epigenetic modification. This information is of potential significance for the identification of therapeutic targets in human choriocarcinoma.