The highly efficient removal of bilirubin from blood by hemoperfusion for liver failure therapy remains a challenge in the clinical field due to the low adsorption capacity and poor hemocompatibility of currently used carbon-based adsorbents. Polysaccharide-based cryogels seem to be promising candidates for hemoperfusion adsorbents owing to their inherited excellent hemocompatibility. However, the weak mechanical strength and relatively low adsorption capacity of polysaccharide-based cryogels limited their application in bilirubin adsorption. In this work, we presented a freezing-triggered strategy to fabricate QCS/MFC cryogels, which were formed by quaternized chitosan (QCS) crosslinked with divinylsulfonyl methane (BVSM) and reinforced with microfibrillated cellulose (MFC). Ice crystal exclusions triggered the chemical crosslinking to generate the cryogels with dense pore walls. The obtained QCS/MFC cryogels were characterized by FTIR, SEM, stress-strain test, and hemocompatibility assay, which exhibited interconnected macroporous structures, excellent shape-recovery and mechanical performance, and outstanding blood compatibility. Due to the quaternary ammonium functionalization of chitosan, the QCS/MFC showed a high adsorption capacity of 250 mg g-1 and a short adsorption equilibrium time of 3 h. More importantly, the QCS/MFC still exhibited high adsorption efficiency (over 49.7%) in the presence of 40 g L-1 albumin. Furthermore, the QCS/MFC could also maintain high dynamic adsorption efficiency in self-made hemoperfusion devices. This facile approach provides a new avenue to develop high-performance hemoperfusion adsorbents for bilirubin removal, showing great promise for the translational therapy of hyperbilirubinemia.