In this study, nutrients digestibility and growth performance of Nile tilapia (Oreochromis niloticus) fed on oilseed meals with crude papain enzyme were determined. A control diet (D1) of 30% crude protein (CP) was formulated using fishmeal (FM), soybean meal (SBM), canola meal (CM) and sunflower meal (SFM). The test diets were formulated with replacing 10% CP of FM by SBM (D2), CM (D3) and SFM (D4), respectively.Crude papain enzyme in powder form was incorporated at 0.06%. Digestibility trial was performed using chromium oxide as an inert marker. A feeding trial of 101 days was conducted using a 4 × 2 factorial design with 4 diets (D1, D2, D3 and D4) and 2 papain enzyme inclusion levels at 0.06% and 0% using 720 Nile tilapia fingerlings (7 ± 3 g). The fingerlings were randomly distributed into 8 groups of 3 replicates of 30 fingerlings per net hapa (2 × 1 × 1 m 3 ). Fish were fed twice daily at 5% of their biomass at 10 AM and 4 PM in two equal meals. Apparent digestibility coefficients increased (p < 0.05) on crude papain enzyme supplementation. There was increase in final body weight (47.32 ± 2.10 g) on 0.06% enzyme than without enzyme (0%) (46.17 ± 2.14 g) (p > 0.05). Irrespective of enzyme supplementation, fish fed FM-based diet were larger (56.89 ± 1.37 g) (p < 0.05) than those fed on oilseed meals; SBM (45.59 ± 0.91 g), CM (43.89 ± 2.12 g) and SFM (40.59 ± 1.60 g). Based on the study, 0.06% crude papain enzyme inclusion increased nutrients digestibility and growth performance of Nile tilapia. Therefore, crude papain enzyme is recommended as a feed additive in Nile tilapia diets to promote growth. However, more research is recommended to determine optimum inclusion levels of crude papain enzyme in Nile tilapia diets.