Clustering pony-size nanocrystals into secondary structures (colloidal nanocrystal clusters, CNCs) not only combines the properties of primary nanocrystals, but also obtains the novel functions originated from the strengthened interactions between neighboring nanocrystals. Herein, we use the PtNi clusters and CeO2 clusters as the primary subunits to construct the PtNi/CeO2 CNCs, which can enhance the interaction between PtNi and CeO2 clusters, as well as improve the electron conductivity of CeO2 originated from the strengthened attachment. Plenty of grain boundaries and lattice distortion generated after introducing the CeO2 clusters into the inner surface of PtNi CNCs, which improves the electrooxidation activity and anti-CO-poisoning ability of PtNi/CeO2 CNCs. Specifically, the PtNi/CeO2 CNCs exhibited higher specific activities than PtNi CNCs towards electrooxidation reactions of methanol, formic acid and ethylene glycol, as well as 8.5, 7.7 and 7.0 times higher than those of Pt/C, respectively, along with enhanced stability. Combined with the experiments and characterizations, the improved property is originated from the novel functions of grain boundary, subtle lattice distortion and strengthened interaction. This study realizes architectural engineering of CNCs with quite different nanocrystal subunits, and creates an effective strategy for eliminating the disadvantages of conventional Pt/CeO2 catalyst in electrooxidation of liquid fuels.