The addition of P to a Ni/SiO2 catalyst greatly changes the isobutane dehydrogenation performance. The Ni:P ratio is an important influencing factor for a Ni–P/SiO2 catalyst because of the formation of different Ni–P compounds. When the Ni:P ratio equals 1:1, a Ni–P/SiO2 catalyst with Ni2P formed on the surface exhibits an optimum dehydrogenation performance (an isobutane conversion of 22% and an isobutene selectivity of 81.3%). The in situ Fourier transform infrared characterization was performed to determine the adsorption mode of isobutane. Isobutane is adsorbed onto the Ni–P surface with one H atom in a methyl group, and the intermediate tends to form isobutene rather than C–C bond scission. Moreover, the decreased adsorption energy of isobutene on the Ni2P surface inhibits its further reaction. The deactivation of a Ni–P/SiO2 catalyst is mainly caused by the phase transformation from Ni2P to Ni12P5 and coke deposition. Finally, some general rules are summarized to get a deep understanding of the second component added to a Ni/SiO2 catalyst.