Objective  To establish a cell model based on calcium-activated chloride channel（CaCC）that could sensitively detect the second messenger Ca²⁺ in the cytoplasm.    Methods  The eukaryotic expression vectors of anoctamin 1(ANO1) and YF-H148Q/I152 L were constructed respectively. FRT cells co-expressing ANO1 and YFP-H148Q/I152 L were obtained by liposome transfection. The expression of ANO1 and YFP-H148Q/I152 L in FRT cells was observed by an inverted fluorescence microscope, and flow cytometry was used to detect the purity of cells. Patch clamp was applied to study physiological characteristics of CaCC. The cell model was identified by the fluorescence quenching kinetics test. The validation of the cell model which could screen CaCC modulators was verified by the fluorescence quenching kinetics experiments. The fluorescent probe was used to detect the calcium concentration in cytoplasm after adding CaCC activator.    Results  The result  of the inverted fluorescence microscope showed that ANO1 was expressed in the cell membrane of FRT, and YFP-H148Q/I152 L was expressed in the cytoplasm of FRT cells. The cell model had the physiological characteristics of classical calcium-activated chloride channels. The FRT cell model stably co-expressing ANO1 and YFP-H148Q/I152 L was successfully constructed. The model could screen CaCC modulators, and the slope of fluorescence change and the concentration of CaCC modulators were in a dose-dependent manner. The slope of the fluorescence could reflect the calcium concentration in the cytoplasm. The cell model can sensitively detect intracellular calcium concentration.    Conclusion  The cell can efficiently and sensitively detect the second messenger Ca²⁺ concentration in the cytoplasm, and it provides a simple and efficient method  for the study of other targets associated Ca²⁺ signal.