Currently, the novel brominated flame retardant, 1,2,5,6-tetrabromocyclooctane (TBCO), is considered as a potential replacement for hexabromocyclododecane (HBCD). As such, use of TBCO could increase significantly in the near future. Therefore, this study investigated the toxicity of TBCO in order to assess its potential toxicological risks to aquatic organisms. Embryos of Japanese medaka (Oryzias latipes) were exposed to 10, 100 and 1,000 μg/L TBCO, and molecular responses were characterized by use of transcriptomics (RNAseq) and proteomics in embryos exposed to 100 μg/L TBCO that were collected on the day of hatch. TBCO was accumulated in embryos by 0.43-1.3×104 30 fold and the rate of accumulation was 1.7-1.8 day-131 . Number of days to hatch and success of hatching of embryos exposed to the two greatest concentrations of TBCO were impaired. Consistent with effects on hatching, proteins that were less abundant were enriched in pathways of embryo development and hatching. Responses of the transcriptome and proteome to TBCO also were used to predict adverse effects of TBCO. Functionally grouped gene ontology terms indicated that TBCO might impair contraction of cardiac muscle and vision, and these effects were confirmed by use of targeted bioassays designed to evaluate cardiac and visual performance. Results of this study provided a comprehensive understanding of effects of TBCO on medaka at early-life stages. Also, the study illustrated the power of “omics” approaches to explain and predict phenotypic responses to the exposure with chemicals.