The introduction of functional groups or oxygen vacancies into Pd-based electrocatalysts is a powerful strategy for enhancing the electrocatalytic performances for many electrocatalytic reactions. Herein, an amorphous ceria-modified Pd nanocomposite anchored on D-4-amino-phenylalanine (DAP)-functionalized graphene nanosheets (Pd-CeO2-x/FGS) was prepared by a facile and effective one-pot synthetic strategy and further used as an electrocatalyst for the ethanol oxidation reaction (EOR) in alkaline electrolytes. The obtained Pd-CeO2-x/FGS exhibits relatively high electrocatalytic activity, fast kinetics and excellent antipoisoning ability as well as robust durability for EOR, outperforming the comparable electrocatalysts as well as commercial Pd/C. The experimental results show that the enhanced EOR properties of Pd-CeO2-x/FGS can be attributed to the DAP-functionalization and CeO2-x-modification. Adequate functional groups (amino and carboxyl groups) and abundant oxygen vacancies were introduced in Pd-CeO2-x/FGS by DAP-functionalization and CeO2-x-modification. The functional groups facilitate the anchoring of small nanoparticles onto the substrate as well as modulate the electron density of Pd. The oxygen vacancies boost the adsorption ability of the reactive oxygen species (OHads) and accelerate the kinetics of the potential-limiting step for EOR. This study proposes a new strategy for the rational design of highly efficient catalysts for the electro-oxidation reaction.