The xylanase production from Thermomyces lanuginosus VAPS-24 has been optimized using OFAT (One factor at a time) approach using agro-industrial substrates. Further, central composite design (CCD) has been employed to optimize various process parameters such as temperature (45-55 degrees C), carbon source concentration (1.5-2.5%), fermentation time (72-120 h) and production medium pH (6-8). Maximum xylanase yield after RSM optimization was approximately double (119.91 +/- 2.53 U mL(-1)) than un-optimized conditions (61.09 +/- 0.91 U mL(-1)). Several hybrid statistical tools such as Genetic Algorithm-Response Surface Methodology (GA-RSM), Artificial Neural Network (ANN), Genetic Algorithm-Artificial Neural Network (GA-ANN) were employed to obtain more optimized process parameters to maximize the xylanase production and observed an increase of 10.50% xylanase production (132.51 +/- 3.27 U mL(-1)) as compared to RSM response (119.91 +/- 2.53 U mL(-1)). The various pretreated and untreated agricultural residues were subjected to saccharification by using crude xylanase in which the pretreated rice straw yielded maximum fermentable sugars 126.89 mg g(-1).