Methyl-CpG binding domain protein 1 (MBD1) is a transcriptional regulator that binds methylated CpG islands of tumor suppressor genes and represses their transcription. In a former study, we found high expression of MBD1 in pancreatic cancer cell lines and tissues which may play an important role in the development of pancreatic cancer. In the present study, we incorporated the siRNA sequence of MBD1 plasmid into a PLGA-poloxamer carrier to test the therapeutic effect of this compound on BxPC-3 human pancreatic cancer cells. We found that an MBD1 siRNA plasmid can be successfully transfected into tumor cells and the MBD1 nanoparticle compound can inhibit cell growth and induce apoptosis. The MBD1 nanoparticle is a promising candidate for gene therapy of pancreatic cancer in vitro.