A water-stable and pH-independent sensor for qualitative and quantitative detection of nicotine in urine solution and living cell was successfully developed. This material, named MB@UiO-66-NH2, can be synthesized by encapsulating methylene blue (MB) with a well-known metal-organic framework (MOF) UiO-66-NH2 through a simple impregnation method. The fluorescence intensity of the system was significantly enhanced when a certain amount of nicotine was added. In the meanwhile, MB is reduced by reductive nicotine to form leucomethylene blue (LB). The proposed sensor displayed excellent selectivity and sensitivity toward nicotine with LOD (limit of detection) of 0.98 µM, which is comparable or even better than that of the electrochemistry detecting methods for nicotine. The obvious enhancement and blue shift of the emission arise from the photoinduced electron transfer (PET) from LB to the UiO-66-NH2. The photophysical properties and the sensing applications of MB@UiO-66-NH2 suggest that this composite can be acted as a sensitive, selective, recyclable and fluorogenic sensor for nicotine determination in urine solution and living cell.