There is a need to formulate new insecticides against insect-borne diseases. Silica nanoparticles (SNPs) prepared by sol–gel ( A800) and sol–gel/combustion ( B800) methods were tested at different concentrations of 5, 25, 50, 100, and 200 ppm after 24 and 48 h on Culex pipiens larvae. The synthesized SiO2 was characterized by using different spectroscopic techniques. Our data revealed that silica nanoparticles ( B800) showed high larvicidal activity as the LC50 values were 19.7, 37.4, 61.1, and 85.2 for the 1st, 2nd, 3rd, and 4th larval instar and 234.8 ppm for the pupal stage at 24 h, respectively. A higher mortality percentage was observed in the 1st larval instar than in all the other immature life stages treated with silica nanoparticles. At 200 ppm, the mortality reached 100% and 90% on treating mosquitoes with B800 and A800 silica nanoparticles, respectively for the1st larval instar compared to 81.7% and 63.3% for the 4th larval instar at 24 h. On treatment with an LC50 concentration of the B800 and A800 silica nanoparticles, the larvae took 22.7 and 18.4 days respectively, compared to 13.3 days for the control, to reach the pupal stage. Glutathione-S-transferase and α-esterase activities increased significantly after treatment with the LC50 concentration of SNPs ( A800 &B800). Conversely, alkaline/acid phosphatase enzyme activity and total protein were reduced. We suggest the use of silica nanoparticles in mosquito control as an eco-friendly approach.