Chronic　lymphocytic　leukaemia　(CLL)　is　a　rare　blood　cancer　that　always　relapses　as　refractory　disease　and　eventually　leads　to　death.　To　date,　therapeutic　options　for　CLL　patients　are　scarce　and　there　is　an　urgent　need　to　develop　novel　chemotherapeutics　that　are　both　effective　and　safe.　Gold-containing　compounds　induce　a　lethal　oxidative　and　endoplasmic　reticulum　stress　response　in　cultured　and　primary　CLL　cells　via　inhibition　of　thioredoxin　reductase　(TrxR).　However,　traditional　gold-containing　medicines　have　revealed　side　effects　during　clinical　applications.　Therefore,　safer　gold-containing　drugs　are　needed　to　overcome　this　challenge.　In　this　study,　a　novel　peptide　templated　gold　cluster　Au25Sv9　was　synthesized　and　its　therapeutic　effect　on　CLL　cells　was　evaluated.　This　nanocluster　could　induce　cell　apoptosis　in　MEC-1　cells　in　a　dose-dependent　manner　which　correlated　with　the　uptake　amount　of　clusters　in　cells.　As　expected,　increasing　intracellular　reactive　oxidative　species　(ROS)　in　MEC-1　cells　was　exhibited　with　the　increase　of　cluster　dosage.　Further　analyses　demonstrated　the　underlying　mechanism　that　the　nanoclusters　suppress　the　activity　of　TrxR1,　increase　the　level　of　intracellular　ROS,　destroy　the　mitochondrial　membrane　potential　and　finally　trigger　the　mitochondrial　apoptotic　pathway　in　MEC-1　cells.　Furthermore,　the　direct　interaction　between　Au25Sv9　clusters　and　TrxR1　was　confirmed　for　the　first　time　by　isothermal　titration　calorimetry.　These　findings　explored　the　preclinical　efficacy　and　potential　mechanism　of　gold　clusters　in　CLL　therapy　and　provided　a　fundamental　reference　for　the　development　of　other　novel　gold-containing　chemotherapeutics　to　treat　CLL.　(C)　2017　Science　China　Press.　Published　by　Elsevier　B.V.　and　Science　China　Press.　All　rights　reserved.