The use of silicon in nutrition has drawn attention from all around the world in recent decades, but little is known about how it affects fish nutrition and metabolism. The aim of the study was to assess how dietary supplementation with organic silicon affected the hybrid Tilapia (Oreochromis mossambicus × Oreochromis niloticus) in terms of growth performance, blood biochemistry, digestive enzymes, morph histology, intestinal microbiota, and stress resistance. Though little is known about how silicon affects fish nutrition and metabolism, the use of silicon in nutrition has garnered attention in recent decades from all around the world. The study's objective was to evaluate the effects of nutritional supplementation with organic silicon on the growth performance, blood biochemistry, digestive enzymes, morphohistology, intestinal microbiota, and stress tolerance of hybrid Tilapia (Oreochromis mossambicus × Oreochromis niloticus). The 16S rRNA gene sequencing analysis of the gut microbiota showed a high diversity and richness of OTU/Chao-1, with Fusobacteria, Proteobacteria, Bacteroidetes and Acid bacteria predominating in the DOS treatments compared to the control (p<0.05). Induction of hypoxia stress after the feeding period showed a significant relative survival rate of 83.33% in fish fed 50 mg·kg−1 . It is concluded that the DOS treatments performed better than the control treatment in most of the variables analysed. DOS had no negative effects on the fish. The results showed that up to 50 mg·kg−1 DOS improved digestive, metabolic and growth performance in hybrid Tilapia.