The exact mechanism of preeclampsia (PE) remains unclear, accumulating researches have indicated multiple epigenetic factors relate to PE and histone methylation plays a crucial role in modifying the gene expression. So we aimed to confirm that abnormal expression of histone demethylase JHDM1D contributes to PE and lower expression of HLA-G in PE. We tested the expression of JHDM1D, H3K9me2, and H3K27me2 in the placentas of PE and normal control (NC)women who had a healthy pregnancy with Immunohistochemistry and we found that JHDM1D, H3K9me2, and H3K27me2 were all mainly expressed in the nuclei of the extra-villous trophoblasts (EVTs). JHDM1D was lower expressed in PE than in NC placentas, corresponding with the mRNA level and protein level with qTR-PCR and western blot, while H3K9me2 and H3K27me2 were higher expressed in PE. We further investigated the biological functions of JHDM1D in HTR-8/SVneo cells. We found that siJHDM1D inhibited cell growth after 24 h of the transfection and reduced the invasion, while increasing the apoptosis of HTR-8/SVneo. We then constructed the siJHDM1D stable cell line and confirmed with CHIP-qPCR that siJHDM1D inhibited the expression of HLA-G through increased the enrichment of H3K9me2 and H3K27me2 in the JHDM1D bounding region of HLA-G. Taken together, our study confirms that decreased expression of JHDM1D is associated with PE through down-regulating HLA-G and casts new light to the diagnosis and therapy of PE.