[en] Highlights: • Clioquinol inhibits the fibril formation of hen egg-white lysozyme. • The binding between clioquinol and hen egg-white lysozyme prevents the exposure of hydrophobic regions. • Clioquinol retards the conversion of α-helix to β-sheet of hen egg-white lysozyme. Here, we reported the role of clioquinol in amyloid aggregation of hen egg white lysozyme (HEWL) under stressful conditions by several biophysical methods including thioflavin-T (ThT) fluorescence, Congo red (CR), circular dichroism (CD) and transmission electron microscopy. Our work showed that CQ inhibited the fibril formation of HEWL and the inhibitory effects depended on the concentrations of CQ. Furthermore, fluorescence spectra were used to study the conformation changes of HEWL caused by CQ. These data revealed that the interactions of CQ with HEWL changed the tertiary structure and inhibited the hydrophobic exposure of HEWL.