In this study, carboxymethyl cellulase was produced in submerged fermentation characterized and saccharification was optimized through Box-Behnken design. The optima pH and temperature of enzyme produced by Trichoderma viride were 5 and 50 oC, respectively. The crude enzyme had Km and Vmax values of 1.5143 µM and 0.9253µM/min, respectively, using carboxymethyl cellulose as substrate respectively. Three variables including pH (X1), incubation temperature (X2) and substrate concentration (X3) with three levels were used to optimize saccharification of wheat straw having 83% cellulose content using Box Behnken design and Artificial Neural Network (ANN). Results reveal that the proposed model was significant and quadratic effect of these parameters significantly affects the sugar production. Maximum sugar production (28.87 mg/ml) was predicted at RSM predicted levels of pH (6.6), incubation temperature (50 ºC) and (6.2%) substrate concentration, while the levels predicted for pH, temperature and substrate concentration were 5, 50 oC and 3.5 %, respectively, by ANN. The predicted sugar concentration at these levels was 30.72 mg/mL. The observed values at the predicted levels of RSM and ANN were 25.52 and 29.95 mg/mL respectively.