Abstract Enzyme-catalyzed biodegradation is an emerging green strategy for environmental remediation, although challenged by high cost and poor robustness. Herein, natural biopolymer (cellulose)-derived hydrogels concurrently doped with β-cyclodextrin and montmorillonite nanosheets that are synthesized in one-step demonstrate exceptional pollutant affinity and mechanical strength. Laccase is then stably and effectively assembled onto the hydrogels by a facile strategy based on charge-assisted H-bonding, which can be extended to other enzymes. The advanced laccase-assembled hydrogels display excellent stability and increased degradation activity achieved by strong substrate capture and rapid electron transfer. The laccase-assembled hydrogels exhibit significantly improved removal (62-fold) and degradation (52-fold) performance compared to free laccase for diverse organic pollutants (e.g., polycyclic aromatic hydrocarbons) in real wastewater. This enhanced performance is maintained despite the presence of heavy metals, other organic chemicals or dissolved organic matter. This work provides a practical strategy for designing an advanced and sustainable biodegradation tool for environmental remediation.