We found that inhibition of SIRT1 enhanced susceptibility of various human MDR cancer cells to Hsp90 inhibitors, possibly through down-regulation of Hsp70/Hsp27 and P-gp and reduction of P-gp-mediated efflux activity, suggesting that Hsp90 inhibitors would exert effective therapeutic activity on MDR cells in combination with SIRT1 inhibitors. Here, SIRT1 is linked to cancer.