Herein, the quenching method was employed to prepare ultra-low loading high-entropy catalyst for highly active, chemoselective, and robust furfural hydrogenation. The metals (Pd, Pt, Ru, Mo, Zn) in the form of a complex were vacancy anchored and strongly interacted with the support (TiO2) during the quenching and reduction process, ultimately forming the high entropy catalyst PdPtRuMoZn-TiO2 with strong metal and support interaction (SMSI) driven encapsulated layer. Moreover, this catalyst exhibits excellent catalytic performance for furfural selective hydrogenation with 90.82% conversion and 91.3% selectivity toward furfuryl alcohol at ambient temperature. The catalytic mechanism showed that high-entropy alloy (HEA) enhanced the hydrogen dissociation and migration capacity, and adjusted the electron environment of the interface between TiO2 and HEA, causing rich oxygen vacancies in the TiO2 SMSI driven encapsulated layer and the reduction of the horizontal furfural adsorption configuration, resulting in high FF conversion and furfuryl alcohol selectivity. The work reported ultra-low loading high-entropy catalyst and their superior performance in bio-cellulose-derived product conversion.