Cellulose is commonly believed to be inactive to organic substances; this inertness is an essential requirement for raw materials in industrial products. Here, we demonstrate the contradictory but promising properties, which are the hydrolytic activities of crystalline cellulose nanofibers for the ester, monophosphate, and even amide bonds of small organic substrates under extremely mild conditions (neutral pH, moderate temperature, and atmospheric pressure). The hydrolytic activities were signficantly extended to decompose the coat proteins of model viruses, followed by a drastic decrease in their infection capabilities to the host cells.