Selective reduction of 5-hydroxymethylfurfural (HMF) to valuable 2,5-bis(hydroxymethyl)tetrahydrofuran (BHMTHF) remains a significant challenge under mild conditions. The synergistic effect between metal single atoms (SAs) and nanoparticles (NPs) can greatly enhance catalytic activity. Here, a high-performance Pd SAs catalyst supported on N-doped carbon (PdSAs/NC) was developed from Pd@UiO-66-NH2. It was found that partial Pd SAs were spontaneously restructured into Pd NPs during the reaction. Our catalyst exhibited 100% conversion of HMF and 98% selectivity towards BHMTHF at temperature as low as 0 °C. In situ FTIR spectra results and density functional theory calculations indicate that Pd SAs contribute to the C = O activation, while Pd NPs facilitated the H2 dissociation into H* atoms, resulting in synergistic catalytic activity between Pd SAs and Pd NPs.