Naringinase has attracted a great deal of attention in recent years due to its hydrolytic activities which include the production of rhamnose and prunin and debittering of citrus fruit juices. Screening of fifteen marine-derived fungi, locally isolated from Ismalia, Egypt, for naringinase enzyme production, indicated that Aspergillus niger was the most promising. In solid state fermentation (SSF) of the agroindustrial waste, orange rind was used as a substrate containing naringin. Sequential optimization strategy, based on statistical experimental designs, was employed to enhance the production of the debittering naringinase enzyme. Effects of 19 variables were examined for their significance on naringinase production using Plackett-Burman factorial design. Significant parameters were further investigated using Taguchi's (L16 4 5 ) orthogonal array design. Based on statistical analysis (ANOVA), the optimal combinations of the major constituents of media for maximal naringinase production were evaluated as follows: 15 g orange rind waste, 30 mL moisture content, 1% grape fruit, 1% NaNO 3 , 0.5% KH 2 PO 4 , 5 mM MgSO 4 , 5 mM FeSO 4 , and the initial pH 7.5. The activity obtained was more than 3.14-fold the basal production medium.