The interlayer space of layered Ni-Zn mixed basic salt (NiZn) can be controlled precisely by the intercalation of various carboxylate anions with long alkyl chains via simple anion exchange. Expansion of interlayer space in the anion-exchanged NiZn depends on the alkyl chain lengths of pillar molecules. The butyrate anion-exchanged NiZn (C3H7COO-/NiZn) catalyst promoted effectively various base-catalyzed Knoevenagel reactions in water with remarkably high yield. This C3H7COO-/NiZn catalyst was reusable without any loss of catalytic activity or selectivity.