Abstract: An experiment was conduced to evaluate the inclusion of Distillers Dried Grains with Solubles (DDGS) in commercial layer diets with Avizyme 1500® supplementation. Two hundred eighty-eight 40-week-old Bovans brown layers were distributed in a completely randomized experimental design in a 2 x 4 factorial arrangement, with the variables being (DDGS) substitution for soybean meal at four levels (0 or 25% or 50% or 75%) and Avizyme 1500 at two levels (0 or 0.075%). Layer performance, egg quality, nutrients digestibility and blood parameters were evaluated. Results showed that average egg production, egg weight, egg mass, feed conversion ratio and the change in body weight of laying hens were significantly (p<0.05) decreased as dietary inclusion of DDGS increased. Avizyme supplementation relatively improved (p<0.05) egg production, egg mass and feed conversion ratio for DDGS inclusion levels at 25 and 50% when compared to those fed diets without Avizyme supplementation. No significant effect of DDGS, Avizyme, or their interaction on feed intake was observed. Yolk color was significantly increased, when DDGS was included in the diet. No significant differences in digestion coefficient values of Dry Matter (DM), Organic Matter (OM), Ether Extract (EE) and Nitrogen Free Extract (NFE) while, there were significant differences (p<0.05) for Crude Protein (CP) and Crude Fiber (CF) digestibility. Dietary inclusion of DDGS without Avizyme linearly reduced cost of feed. Although Avizyme supplementation increased the cost per kilogram of formulated diet, but improves economical efficiency value. The results suggest that diets containing DDGS at less than 15.45% level (50% of SBM) with Avizyme 1500® supplementation could improve the nutritive value of DDGS for layers.