The first example rotaxane@MOF (named as CUST-761) has been designed and constructed via combining CB[6]-based rotaxane ([PR44] 2+ •2[NO 3 ] − ), 4,4′-biphenyldicarboxylate sodium salts (Na 2 BPDC), and transition metal cadmium ion under solvothermal conditions. X-ray single crystal diffraction revealed CUST-761 exhibits a two-dimensional (2D) layered structure where rotaxanes are well embedded in the crystal lattices formed by BPDCs and cadmium ions. Thermogravimetric analysis (TGA) and Powder X-ray diffraction (PXRD) showed that CUST-761 possesses excellent stability. The utility of CUST-761 as fluorescence sensors has also been discussed. The results indicated that CUST-761 can be used as a multiresponsive fluorescence sensor for detecting Fe 3+ and Cr 2 O 7 2− with good sensitivity, high selectivity, and recoverability, even in the presence of other interfering ions. Besides, CUST-761 also can selectively detect nitrofurantoin. The mechanism of CUST-761 as a multiresponsive fluorescence sensor for detecting Fe 3+ , Cr 2 O 7 2− , and the antibiotic nitrofurantoin has been clarified by experiments and theoretical calculations. This work provides insights into the design and synthesis of fluorescence sensing crystalstate materials.