The aim of the present study was to determine whether quercetin, an antioxidant and radical scavenger as natural flavonoid, would be able to offer any protection against cadmium (Cd) toxicity in olive flounder, Paralichthys olivaceus with emphasis on biochemical analysis. Fish were pre-treated with 0% (Diet 1), 0.25% (Diet 2) and 0.5% (Diet 3) quercetin for 30 and 60 day and after that, fish were post-exposed to 10 ppb Cd for 0, 6, 12, 24, and 48 hr. To understand the stress-resistance effect of quercetin, we measured the mRNA expression of metallothionein (MT), glucocorticoid receptor (GR), and level of acetylcholinesterase (AChE) in quercetin-treated flounder exposed to Cd. The MT and GR expression levels were lower in flounder fed Diets 2 and 3 than in those fed Diet 1, and AChE level was higher in flounder fed Diet 2 and 3 than in those fed Diet 1. Plasma cortisol increased in fish fed Diets 1, 2, and 3, but it was lower in fish fed Diets 2 and 3 than in those fed Diet 1. In addition, lipid peroxidation (LPO) levels lower than with Diet 1, which protected the cell membrane. We also investigated the effects of cortisol on stress resistance in vitro. Results showed that the MT and GR expression levels were lower in livers of flounder fed with Diets 2 and 3 than those fed with Diet 1, suggesting that quercetin reduced the stress induced by Cd. These results indicate that quercetin has a stress-resistance effect and acts to maintain physiological homeostasis.