Fabrication of catalysts based on metal nanoclusters has attracted intensive research attention due to their superior catalytic activity. Herein, two three-dimensional hydrophobic porous organic polymers (3D-HPOPs-1 and 3D-HPOPs-2, respectively) that exhibited high specific surface areas and unique microporous-mesoporous structures were fabricated. Ultrafine Pd nanoclusters were successfully confined into the N atoms containing cages of 3D-HPOPs via impregnation and subsequent reduction. Besides, the 3D-HPOPs exhibited excellent hydrophobicity, thus can preferentially adsorb and enrich organic reactants in the pores of the catalyst, this in turn leads to the catalytic reaction as only in the organic phase. High conversion and selectivity were observed for the catalytic hydrogenation of nitroarenes over as-obtained Pd(0.7%)@3D-HPOPs-1 in water under mild reaction conditions. Moreover, the prepared catalyst can be easily recovered and reused without loss of activity. This study may provide a feasible strategy for fabricating noble-metal-nanocluster-based catalysts for various reactions under mild and environmentally friendly conditions.