Suitable metal-support interaction is of great significance for the supported Fischer-Tropsch catalyst. Herein, we synthesized a series of porous spinel MAl2O4 (M = Co, Mg, Zn) together with Al2O3, via a sol-gel method and used them as supports for the Co-based Fischer-Tropsch synthesis (FTS) catalyst to investigate the influence of metal-support interaction on Co dispersity, reducibility, and catalytic performance. The catalytic performance showed that 15Co/CoAl2O4 had the highest activity and C5+ selectivity, as well as favorable stability during 1000 h lifetime testing. The catalysts were characterized by physisorption, chemisorption, HRTEM, XPS, and TPSR. The results to, indicated that 15Co/CoAl2O4 showed weaker metal-support interaction ( selectivity than 15Co/MgAl2O4 and 15Co/Al2O3, which was considered as the key factor for its higher reducibility and CO dissociation ability, contributing to the higher CO conversion. The higher Co dispersity on CoAl2O4 resulted from the smaller particle size of Co species on CoAl2O4, contributing to the higher activity of 15Co/CoAl2O4 than that of 15Co/ZnAl2O4. The higher C5+ selectivity on 15Co/CoAl2O4 and 15Co/ZnAl2O4 than that on 15Co/MgAl2O4 and 15Co/Al2O3 was verified to benefit from the appropriate H-2/CO adsorption ability, which was significantly affected by metal-support interaction.