A method is proposed for the sulfation of microcrystalline cellulose in the system N,N-dimethylformamide/chlorosulphonic acid with preliminary treatment of cellulose with ultrasound in an organic solvent. It is demonstrated that the treatment with ultrasound results in an increase in the reactivity of cellulose in the sulfation reaction as well as in occurring the sulfation in homogeneous medium. The action of ultrasound on microcrystalline cellulose is accompanied by a decrease in the polymerization level of the cellulose material and does not affect its crystallinity index. Water-soluble cellulose sulphates with the substitution level up to 1.5 were obtained using the method proposed.