Abstract The understanding of the interaction between the semiconductor nanocrystals (NCs) and the proteins are essential for design and fabrication of nanocomposites for application in the field of biotechnology. Herein, we have studied the interaction between CdTe NCs and the proteins by steady-state and time-resolved photoluminescence (PL) spectroscopy. The steady-state PL intensity of CdTe NCs is quenched and enhanced in the presence of lysozyme and bovine serum albumin, respectively. However, the PL intensity of CdTe NCs is not affected with α-synuclein, indicating the role of tryptophan moiety in the protein–NCs interaction. The detailed analysis of PL data allows us to elucidate the dominant mechanism of interaction, i.e. charge or energy transfer, depending on the location of tryptophan residues in the protein. Assuming a Poisson statistic of lysozymes around NCs, the Poisson binding model is used to understand the kinetics of charge transfer from CdTe NCs to the lysozyme. It provides the average number of lysozymes present on the surface of one CdTe NC.