Quercetin (3,3 ′,4 ′,5,7-pentahydroxyflavone), a ubiquitous, bioactive plant flavonoid, is known to possess anti-cancer, anti-tumor, and other important therapeutic activities of significant potency and low systemic toxicity. In this communication, we report for the first time a study on the interactions of quercetin with the plasma protein human serum albumin (HSA), exploiting the intrinsic fluorescence emission properties of quercetin as a probe. Quercetin is weakly fluorescent in aqueous buffer medium, with an emission maximum at ≈538 nm . Binding of quercetin with HSA leads to dramatic enhancement in the fluorescence emission intensity and anisotropy ( r), along with significant changes in the fluorescence excitation and emission profiles. The excitation spectrum suggests occurrence of efficient Förster type resonance energy transfer (FRET) from the single tryptophan-214 residue of HSA to the protein bound quercetin. The emission, excitation, and anisotropy ( r=0.18 at [ HSA]=30 μ M) data (using the native protein) along with emission studies of quercetin using partially denatured HSA (by 8 M urea) indicate that the quercetin molecules bind at a motionally restricted site near tryptophan-214 in the interdomain cleft region of HSA. Furthermore, the binding constant ( K=1.9×10 5 M −1 ) and Gibbs free energy change ( ΔG 0=−30.12 kJ/ mol) ) for quercetin–HSA interaction have been calculated from the relevant anisotropy data. Implications of these results are examined, particularly in relation to prospective applications in biomedical research.