This paper demonstrates the synthesis of ZnAl(NO3)-layered double hydroxide (LDH) nanoparticles based on an experimental design method. The response surface methodology (RSM) was developed as experimental strategies for modeling and optimization of the influence of some variables on the synthesis of LDH. Twenty experiments were carried out for determining the conditions of reactions by the central composite design (CCD) technique. The quantitative variables such as pH, temperature, and reaction time and the qualitative variables including the type of salts and solvents were considered in preparation of LDHs. The responses were average thickness of LDH particles and height of the X-ray diffraction (XRD) patterns.