In this work, Ni/Ca/Al LDH catalyst with M2+/M3+:3/1 molar ratio was synthesized by co-precipitation method in constant pH and calcined subsequently. The Ca/Al LDH catalyst was also synthesized by similar method and was compared to Ni/Ca/Al sample. These catalyst samples were characterized by XRD, SEM, FTIR, and BET techniques. The results of the XRD, and SEM analysis show the nanoparticles of Ni/Ca/Al mixed oxides were synthesized successfully. In order to determine the catalytic activity of synthesized samples in the industrial organic reactions, the Knoevenagel condensation reaction between diethyl malonate and benzaldehyde was performed over these samples, and it was found that the Ni0.5/Ca2.5/Al catalyst is very efficient for such reactions.