Raf kinase inhibitor protein (RKIP), an inhibitor of Raf-mediated activation of mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK), has been identified as a metastasis suppressor gene. However, the role of RKIP in human choriocarcinoma remains undetermined. Therefore, in the present study, we investigated the expression of RKIP in human choriocarcinoma cells and evaluated the effects of RKIP on choriocarcinoma cell proliferation and invasion. Our results indicated that RKIP was lowly expressed in human choriocarcinoma cells. Overexpression of RKIP inhibits choriocarcinoma cell proliferation, migration and invasion, promotes the apoptosis of choriocarcinoma cells. Furthermore, overexpression of RKIP significantly inhibited the expression of MEK and ERK phosphorylation in choriocarcinoma cells. Taken together, these data suggest that RKIP suppresses cell proliferation and invasion in choriocarcinoma cells through inhibiting the MAPK signaling pathway, implying that RKIP may serve as a potential molecular target for the treatment of human choriocarcinoma.