In this study, the transgenerational effects of polystyrene nanoplastics (PS-NPs) and ethylhexyl salicylate (EHS), and their interactive effects on zebrafish (Danio rerio) were investigated. It was found that EHS concentrations in F0 and F1 in co-exposure groups were higher than those in single exposure. The hatching rates of F0 and F1 decreased and the malformation and mortality rates of F1 increased, especially in co-exposure groups. For F0, antioxidant indicators (including glutathione, reactive oxygen species and malondialdehyde contents, and superoxide dismutase and catalase activities) and thyroid indicators (e.g. triiodothyronine contents and thyroid receptor A, thyroid receptor B and deiodinase 2 expression levels) in all test groups containing EHS were all increased, while the thyroxin content and deiodinase 1 expression levels were reduced compared with the corresponding control group. F1 showed similar or even stronger biochemical effects, while the indicators mentioned above for F0 and F1 in co-exposure groups were further intensified on the basis of EHS alone. Our results showed that the presence of PS-NPs may promote the bioaccumulation of EHS and its transfer from parents to offspring. EHS could induce growth and developmental toxicity, oxidative stress and thyroid toxicity on both parents and offspring, while PS-NPs and EHS exerted interactive effects on the transgenerational effects of EHS on zebrafish. Ultimately, two associated potential adverse outcome pathways of transgenerational toxicity were identified in EHS and PS-NP co-exposure: 1) destruction of thyroid hormone homeostasis; 2) generation of reactive oxygen species and malondialdehyde.