A three-factor, three-level Box-Behnken Design (BBD) was used with enzyme dosage (0.05-0.15‰ o.d. fiber), enzymatic contact time (20-40 min), and pulp consistency (3-7%, o.d.) as independent variables to understand and optimize the enzymatic pretreatment conditions of mixed office waste (MOW) for maximum improvement of its drainability. All the independent variables considered were found to have significant influence on the drainability of the pulp. The enzyme dosage had a predominate effect, the pulp consistency took second place, and the contact time seemed to have low priority. A quadratic polynomial model had high Adj-R2 value and low p value for predicting the decrement of beating degree of the pulp. Applying desirability function method, the optimal pretreatment conditions were found to be an enzyme dosage of 0.11‰ o.d., enzymatic contact time of 31.0 min, and pulp consistency of 4.50% o.d. The optimal pretreatment resulted in a maximum decrement of 10 units of beating degree, a decrease by 20% when compared with the control sample. The observed and predicted values of beating degrees were in close agreement. Results of fiber morphology analysis and physical property tests showed that the optimal pretreatment partially recovered the fiber flexibility and retained the strength properties of the handsheet even under the lower beating degree. Isothermal (Thermogravimetric Analyzer) TGA experiments of the fibers confirmed that the enzymatic pretreatment decreased the fiber hornification.