The interaction of pentafluoropropionic acid(IPC-PFFA-3) with human serum albumin(HSA) was studied using molecular docking,molecular dynamics(MD) simulation,fluorescence spectroscopy,synchronous fluorescence and competition experiments.The results of the molecular docking indicated that the binding force between IPC-PFFA-3 and HSA was hydrogen bond.Fluorescence data revealed that the fluorescence quenching of HSA by IPC-PFFA-3 was a static quenching procedure.The thermodynamic parameters showed that binding was spontaneous and was driven mainly by hydrogen bond.Competitive drug displacement results suggested that the binding site of IPC-PFFA-3 with HSA lie on Sudlows site Ⅱ.The experimental results were supported by the molecular docking.MD and synchronous fluorescence suggested that HSA does have a sight conformational change when it binds with IPC-PFFA－3 and the structure of HSA-IPC-PFFA-3 is very stable.