Silicon dioxide nanoparticles (n-SiO2) absorb tetrabromobisphenol A (TBBPA) and modify its bioavailability and toxicity in the aquatic phase; embryonic chorion is an efficient barrier against nanoparticles (e.g., SiO2) and influences their toxicity. However, few studies have investigated developmental neurotoxicity in fish after co-exposure to TBBPA and n-SiO2, especially considering the barrier function of the chorion. In the present study, zebrafish embryos were exposed to TBBPA (50, 100, and 200 μg/L) alone or in combination with n-SiO2 (25 mg/L) until 24 or 120 h post fertilization (hpf), in the presence and absence of the chorion. The results confirmed that TBBPA exposure alone significantly downregulated the expression of neurodevelopment marker genes (mbp, alpha-tubulin, shha, and gfap), altered acetylcholinesterase activity and acetylcholine content, and affected locomotor behavior at different developmental stages. Moreover, the results indicated that n-SiO2 promoted TBBPA-induced neurotoxic effects in zebrafish larvae at 120 hpf, including further repression of the transcription of CNS-related genes, disruption of the cholinergic system, and decrease in the average swimming speed under dark/light stimulation. However, scanning electron microscopy/energy dispersive spectroscopy analysis revealed that at 24 hpf, the embryonic chorion efficiently blocked n-SiO2 and consequently decreased the bioaccumulation of TBBPA and TBBPA-induced neurotoxicity in dechorionated zebrafish embryos. Taken together, the results demonstrate that n-SiO2 affected the bioavailability and neurodevelopmental toxicity of TBBPA, and their combined toxicity to zebrafish embryos was mitigated by embryonic chorion, which will facilitate risk assessment on n-SiO2 and TBBPA and improve understanding the function of the fish embryonic chorion.