The present study shows that NSAIDs such as CCB and IBU significantly potentiate the sensitivity of MDR cells to Hsp90 inhibitors via the autophagic degradation/down-regulation of mutp53 achieved by inhibiting the Akt/mTOR pathway and STAT3/HSF1/P-gp signaling cascades, suggesting that the clinically approved NSAIDs can be used to increase the overall efficacies and utilities of Hsp90 inhibitors through inhibiting the resistance of cancer cells to Hsp90 inhibitors. Here, HSF1 is linked to cancer.