Drug resistance to chemotherapy in cancers remains significant clinical challenges. CD44 modulates cellular adhesion, migration and growth, which plays a pivotal role in driving cancer resistance and even recurrence. Despite ongoing efforts, accurate, safe, and real-time dynamic monitoring techniques for CD44 expression remain inadequate in guiding the management of drug-resistant cancer treatment. In this study, we developed a nano-quenching and recovery detector of CD44 (Cy3-AptCD44@BPNSs) for visualizing cancer drug resistance. The fluorescence recovery of the detector is directly related to the CD44 expression level on cancer cells, which can be used to indicate the degree of drug resistance. It’s confirmed that downregulating CD44 expression on cancer cells results in a corresponding decrease in the fluorescence intensity of the detector, which enables precise and dynamic monitoring of CD44. In addition, the Cy3-AptCD44@BPNSs also exhibited specificity in detecting CD44. This visualizing strategy may open up a wide range of possibilities for rapid recognition to cancer drug resistance, which is more efficient and flexible.