Semiconductor nanoparticles (quantum dots) are promising fluorescent markers, but very little known is about interaction of quantum dots with biological molecules. In this study, interactions of ZnS quantum dots doped with different amounts of Mn (1, 2 and 3 %) with human serum albumin (HSA) were studied by fluorescence and UV–Vis spectroscopic techniques. It was observed that fluorescence of HSA was strongly quenched by ZnS QDs. The results of fluorescence quenching at different temperatures and UV–Vis absorption spectra experiments indicated that the quenching mechanism of serum albumin by QDs is static quenching through formation of the complex of QDs–HSA. According to the modified Stern–Volmer equations at different temperatures, the thermodynamic parameters, Δ H 0 , Δ S 0 and Δ G 0 were determined. The number of binding sites ( n ) was also obtained. It was found that hydrogen bonding and van der Waals interaction played a key role in the interaction process.