Abstract: Mitigation effects of coenzyme Q10 (CoQ10) on spiromesifen (SPM)-induced acute toxicity to zebrafish at different life stages, as well as abnormal development, especially impaired development of heart and notochord, oxidative stress and apoptosis in embryos were investigated using a semi-static method. Results showed that CoQ10 can remarkably reduce the acute toxicity of SPM to zebrafish embryos, larvae and adults by 3.20-, 2.09- and 1.51-fold, respectively. CoQ10 can effectively alleviate the SPM-induced abnormal spontaneous movement, decreased heartbeat, delayed hatching, growth inhibition and various teratogenic effects of zebrafish embryos. At the stage of zebrafish embryo, CoQ10 significantly increases superoxide dismutase (SOD) activity and expression levels of genes related to anti-oxidation (Cat & Cu/Zn-sod), anti-apoptosis (mcl1a & mcl1b), heart development (cmlc1, actc1a & erbb4a) and angiogenesis (vegfaa, vegfd & kdrl), which are inhibited by SPM. Additionally, CoQ10 reduces malondialdehyde (MDA) content and caspase-3 activity of embryos, as well as expression levels of pro-apoptosis (Cas3, Cas9, P53 & bax) and notochord (tbxta & col2a) related genes raised by SPM. The results indicate that CoQ10 can mitigate the acute toxicity of SPM to zebrafish, and alleviate the abnormal development of heart and notochord of embryos by reducing oxidative stress and apoptosis, as well as regulating the expression of related genes.