The　interactions　between　erlotinib　(ET)　and　bovine　serum　albumin　(BSA)　in　the　absence　and　presence　of　Cu(II)　and　Fe(III)　in　aqueous　solution　were　investigated　by　using　fluorescence,　circular　dichroism　and　three-dimensional　(3D)　fluorescence　spectroscopic　methods　under　simulative　physiological　conditions.　Erlotinib　effectively　quenched　the　intrinsic　fluorescence　of　BSA　with　slight　redshifts　in　the　absence　and　presence　of　Cu(II)　and　Fe(III).　Cu(II)　decreased　the　binding　affinity　and　reduced　the　binding　sites　of　erlotinib　to　BSA,　while　Fe(III)　increased　the　binding　affinity　and　binding　sites　of　erlotinib　to　BSA.　The　negative　values　of　ΔH　and　ΔS　illustrate　that　the　binding　is　mainly　driven　by　the　hydrogen　bond　and　van　der　Waals　force.　The　conformation　of　BSA　was　changed　through　ET　binding　in　the　presence　of　Cu(II)　and　Fe(III),　which　was　revealed　by　circular　dichroism,　synchronous　fluorescence　and　3D　fluorescence　spectroscopic　methods.　The　results　indicate　that　the　binding　capability　of　erlotinib　to　BSA　is　affected　by　the　types　of　metal　ions.　©　2012　Elsevier　B.V.　All　rights　reserved.