Rice husks (RHs) was used as a substrate for biosynthesis of high-value Silica nanoparticles (SiO2NPs). An isolate of Trichoderma harzianum MF780864 (T. harzianum) was isolated and identified based on the Internal Transcribed Spacers (ITS) sequences; it showed the potentiality to induce SiO2NPs in the process of RHs biotransformation. SiO2NPs were produced extracellularly and their size was of about 89 nm. SiO2NPs characterized by oval, rod and cubical particles by using Transmission Electron Microscope (TEM).The Fourier transform infrared spectroscopy (FTIR) confirmed the presence of various functional groups of biomolecules and capping protein, encapsulating SiO2NPs. Water and fish samples were collected from private fish farms in El-Sharkia Governorate, Egypt. Lead (Pb) was detected from water and fish samples at its highest concentration at about 0.088 mg/L. The adsorption capacity of Pb by SiO2NPs was evaluated by testing different concentrations of SiO2NPs viz. 1, 2, and 3 mg/L, wherein 1 mg/L revealed the highest Pb adsorption efficiency. Within laboratory trials, the results indicated that highest Pb adsorption efficiency revealed through the increasing of SiO2NPs concentrations until 120 h. In vivo trial that lasted for 8 weeks, Nile tilapia (Oreochromis niloticus) (29.78 ± 0.36 g body weight) supplemented with 0.088 mg/L Pb was divided into four experimental groups having three replicates (15 fish/ replicate; 45 fish/group). The results showed that SiO2NPs supplementation through water revealed significant increase in growth and hematological parameters of O. niloticus. Moreover, enhancement of antioxidant capacity (TAC), and immune related gene expression of IL-1b were increased in the presence of SiO2NPs compared with the groups of Pb exposure. Moreover, Pb residue level in fish muscles was noticeably decreased in the SiO2NPs treated groups. Thus, this research opens up other possibilities in the field of using SiO2NPs as a lead adsorbent for water bioremediation.