In catalysis, tuning the structural composition of the metal alloy is known as an efficient way to optimize the catalytic activity. This work presents the synthesis of compositional segregated six-armed PtCu nanostars via a facile solvothermal method and their distinct composition-structure-dependent performances in electrooxidation processes. The alloy is shown to have a unique six arms with a Cu-rich dodecahedral core, mainly composed of {110} facets and exhibit superior catalytic activity toward alcohols electrooxidation compared to the hollow counterpart where Cu was selectively etched. Density functional theory (DFT) calculations suggest that the formation of hydroxyl intermediate (OH*) is crucial to detoxify CO poisoning during the electrooxidation processes. The addition of Cu is found to effectively adjust the d band location of the alloy catalyst and thus enhance the formation of *OH intermediate from water splitting, which decreases the coverage of *CO intermediate. Our work demonstrates that the unique compositional anisotropy in alloy catalyst may boost their applications in electrocatalysis and provides a methodology for the design of this type catalyst.