A novel selective interlamellar modification of cetyltrimethylammonium bromide-exchanged montmorillonite (MMT) by toluene-2,4-di-isocyanate (TDI) has been successfully obtained, and a polystyrene/TDI-modified MMT hybrid has been prepared. After the interlamellar modification, TDI was grafted to hydroxyl, groups of the MMT, and the orientation of cetyltrimethylammonium in the interlayer space changed from a bilayer lying flat structure to a double-layer inclined one. The structures of the TDI-modified MMT and the hybrid were characterized by Fourier transform infrared (FTIR) spectra, powder X-ray diffraction (XRD), and transmission electron microscopy (TEM) techniques. A schematic model of the TDI-modified MMT structure was also presented.