In recent years, the partial and total substitution of fishmeal (FM) with by-product meals has reduced feed manufactory and aquaculture industry production costs. The present work aimed to determine the effects of the substitution of FM by hydrolyzed feather meal (HFM) in the diet of Macrobrachium tenellum. Four isoproteic and isolipidic diets were prepared, substituting 0, 33, 67, and 100% of FM with HFM. These diets were used to feed M. tenellum juveniles for 60 days. The results of the biological indices, in terms of weight, final length, and specific growth rate, did not show significant differences between the treatments (P ˃ 0.05). The lowest survival index (35 ± 13) is observed in the 100HFM treatment, showing significant differences from the 33HFM treatment (65 ± 13). However, the 67HFM and 100HFM treatments, associated with the lowest values of the biological indices, indicated a decreasing trend. No significant differences were observed in the proximate composition of the muscle between the four treatments. The average values of the four treatments were 33.5% protein, 3.7% lipid, and 18.2% ash. However, the fatty acid profile observed significant differences between the treatments. As the content of HFM increased, the concentration of some fatty acids, such as C14:0, C16:0, C20:5n3, and C22:6n3, decreased, while the content of C18:1n9 and C18:2n6 increased. The results showed that it is feasible to substitute between 33 and 67% of FM with HFM in feed diets for river prawns.