A series of supported Ni-based multifunctional catalysts were prepared and their catalytic performances for n-butanol Guerbet condensation reaction were evaluated. Ni/hydroxyapatite (HAP) shows the best catalytic performance: a selectivity of 2-ethylhexanol reaches 52.4% at an n-butanol conversion of 29.6% at 230 °C. The activity evaluation results indicate that Ni/HAP with both high-density of acid sites and high-density of base sites have higher catalytic performance. Furthermore, the importance of acid-base synergistic catalysis was proved by evaluating the change of the catalytic performance of Ni/HAP catalyst after poisoning the acidic or basic sites using an acid or a base probe molecule.