Nanoparticles (NP) have drawn increasing interest from many fields in medicine and are a relatively new class of biomedical products. Because there are concerns about the health effects of nanoparticles, it is important to understand how nanoparticles interact specifically with red blood cells (RBC), a central object in the blood circulation. As numerous studies that have examined NP/RBC interaction concentrated on the hemolytic potential of nanoparticles, we describe an investigation of hemolytic activity of polystyrene nanoparticles (PS-NP) in protein free medium and its modulation by albumin. We found that treatment of RBCs with PS-NP induces hemolysis (dose and particle size dependent) in plasma free medium but not in full plasma or in buffer, which contain albumin. Critical albumin concentration is 0.05% wt. According to our results hemolytic effect of nanoparticles is strongly modulated by protein concentration in the medium.