Enzymes are the alternative to traditional scouring of cotton fabrics due to their eco-friendly character. The present study focuses on the improvement of bioscouring through the synergistic action of four hydrolytic enzymes at low loadings, thus contributing to the economy of the process. A four factor three level Box-Behnken experimental design was used to investigate the combined effect of pectate lyase (10-60Units/g fabric), lipase (10-40Units/g fabric), protease (5-15Units/g fabric) and xylanase (50-200Units/g fabric) on the physicochemical properties of desized cotton fabrics. Structural features of cotton's cellulose, degree of polymerization and crystallinity index, were not severely affected by enzymatic treatment, while compositional analysis revealed that considerable amounts of non-cellulosic impurities were removed in all treatments. Wetting time (WT), whiteness index (WI) and dye ability (K/S) were the responses selected for simultaneous optimization, with the aid of Derringer's desirability function. The optimum levels of the independent variables pectate lyase, lipase, protease and xylanase were found 60, 10, 11.667 and 140Units/g fabric, respectively. This factor level combination predicted wetting time, whiteness index and dye ability equal to 0.1s, 45.55 Berger degree and 4.79 respectively, which was confirmed through validation experiments. [GRAPHICS] .