The present study was carried out to evaluate the replacement effect of the dietary yellow corn by barley with and without addition of Roxazyme on digestibility, growth performance, feed utilization, and body composition of Nile tilapia (Oreochromis niloticus) fingerlings. A total number of 960 Nile tilapia fingerlings with average body weight 5.36 ± 0.01 g were randomly divided into eight experimental groups (four replicates, 30 fish per each). Eight experimental diets were formulated, the first four diets (T1 W, T2 W, T3 W and T4 W) included 0 (the basal diet), 25, 50 and 100 % barley in place of yellow corn, the other tested four diets (T1 E, T2 E, T3 E and T4 E) were the same previous diets plus150 mg Roxazyme /Kg diet. Results revealed that enzyme addition significantly (P<0.05) improved the digestibility of all nutrients, growth, feed and protein utilization. Also, increased (P<0.05) CP and EE contents in whole fish body significantly, while ash content was significantly (P<0.05) decreased as a result of enzyme addition. On the other hand, increasing the level of barley in the diets significantly (P<0.05) reduced digestibility of DM, CP and NFE. The fish survivability was significantly (P<0.05) improved with 100% barley. Feed intake, growth, and protein utilization significantly (P<0.05) decreased with elevation of barley level in the diets. The moisture, CP and ash contents in whole fish body for 25% barley significantly (P<0.05) increased, while the EE content significantly (P<0.05) decreased compared with 0% barley. Results of interaction between Roxazyme addition and barley level indicated that the DM and NFE digestibility of T2 E was significantly (P<0.05) better than those with the other diets. Growth in T1 E and T2 E did not significantly differed, while feed and protein utilization were significantly (P<0.05) better for T2 E. Results of whole body composition showed significant enhancement (P<0.05) of DM and EE and ash contents of T2 E compared with T2 W. Economically, T2 E recorded the best feed cost per gain. It could be concluded that barley could replace up to 25% of the dietary yellow corn in Nile tilapia fingerling diets with addition of Roxazyme without any adverse effects on growth and feed utilization.