Decabromodiphenyl ethane (DBDPE), one widely used new brominated flame retardant, was of great concern due to its biotoxicity. The toxic evaluation of DBDPE (1–50 mg/L) to white-rot fungus (Pleurotus ostreatus), including oxidative stress, morphology and transcriptomics was conducted aiming at improving its biodegradation. Fungal growth and ATPase activity were obviously inhibited by DBDPE at ≥ 10 mg/L with the exposure from 48 h to 96 h. DBDPE could induce oxidative stress to P. ostreatus. The activity of SOD (superoxide dismutase), CAT (catalase) and GSH (glutathione) were all promoted by DBDPE at ≤ 5 mg/L and inhibited at > 5 mg/L with 96-h exposure. MDA (malondialdehyde) content rose obviously with DBDPE exposure (10–50 mg/L). The mycelium was wizened under 20 mg/L DBDPE exposure according to SEM observation. Transcriptomics analysis suggested that DBDPE could change many functional genes expression of P. ostreatus. GO analysis indicated DBDPE could affect biological process and cellular component by inhibiting electron transport, mitochondrial ATP synthesis, oxidoreductase activity as well as transporter activity. KEGG enrichment pathways analysis indicated DBDPE could inhibit oxidative phosphorylation, tricarboxylic acid (TCA) cycle and carbon metabolism by down-regulating the genes related to NADH reductase/dehydrogenase, succinate dehydrogenase, cytochrome-c reductase/oxidase, cytochrome C1 protein and ATP synthase.