Complex interactions have been established between nanoparticles (NPs) and heavy metals in real environments. Herein we used zebrafish embryos to investigate the influence of titanium dioxide NPs (n-TiO) on the uptake, bioconcentration, and depuration, and toxicity of Pb. The formation of n-TiO-Pb complexes was confirmed in an exposure suspension. An increase in Pb bioconcentration was observed in zebrafish embryos upon co-exposure to n-TiO and Pb; moreover, n-TiO-Pb complexes could be found in the embryos, indicating the bioavailability of NPs. However, there was no difference in the depuration rates of Pb in the presence of n-TiO. Metallothionein (MT) content was significantly increased upon exposure to Pb alone, and the content significantly increased even further upon co-exposure. A downregulation in the expression levels of the neurodevelopment-related genes gfap, syn2α, and elavl3 was observed in the embryos, and we also noted a reduction in the swimming speed of and the total distance traveled by the larvae. To summarize, our results indicate that n-TiO can act as an effective carrier of Pb to enhance its uptake, bioavailability, and toxicity in zebrafish embryos.