Emerging pollutants, such as microplastics (MPs) and polybrominated diphenyl ethers (PBDEs) may pose a serious threat to human health and ecological safety. However, little is known about the MP-mediated PBDEs exposures and their combined toxicities towards farmed fishes. This study investigated the sorption behaviors of two typical PBDEs (BDE-47 and BDE-209) to MPs of different polymer types (PE, PS, PHA and PHB), and examined their combined toxic effects on grouper (Epinephelus moara) by determining the change of oxidative stress markers and comparing gene expression difference through high-throughput sequencing. Our results demonstrated that the sorption of PBDEs on MPs were polymer type-dependent and the sorption capacities were in the order of PHA>PHB>PS>PE. The combined exposures of MPs and PBDEs led to more severe disturbance on the oxidative system compared with individual exposure. The activity of superoxide dismutase (SOD) and the content of glutathione were decreased, while the activity of catalase (CAT) and the content of malondialdehyde were increased. The disorder of oxidative system can influence the growth of groupers. High-throughput sequencing confirmed that pathways of ferroptosis, IL-17 and PPAR expressed differently under combined exposure of MPs and BDE-47. IL-17 pathway related genes were inhibited, while genes in PPAR pathway were upregulated. The combined exposure brought more severe effect on grouper's gene expression compared with individual exposure. GPX-related genes and CAT gene in the liver were up-regulated, while SOD-related genes were down-regulated. Our results demonstrated that the combined toxicity of MPs and PBDEs can pose a non-neglectable threat to aquaculture development and food safety, and gained a primary insight into the potential risk of MPs to farmed fishes.