HD2 proteins were previously identified as plant specific histone deacetylases (HDACs). The molecular mechanism of the function of HD2 proteins is still unclear. Using Bimolecular fluorescence complementation assay, we demonstrated that Arabidopsis HD2 proteins, HD2A, HD2C and HD2D, can interact with RPD3-type HDACs, HDA6 and HDA19, suggesting that that these proteins may act in the same protein complex. Our study indicates that HD2 proteins may functionally associate with RPD3-type HDACs to regulate gene expression in plants.